When try to access unknown type static file, the server return a 404 Not Found error. You can add unknown file type into ContentTypeProvider to support custom file extensions, let browser known how to handle it.

FileExtensionContentTypeProvider provider= new FileExtensionContentTypeProvider();
//these are chemical file types, default provider doesn't contain them
provider.Mappings[".sdf"] = "text/plain";
provider.Mappings[".smi"] = "text/plain";
provider.Mappings[".rdf"] = "text/plain";
app.UseStaticFiles(new StaticFileOptions()
{
	ContentTypeProvider = provider,

	// unknown file type will be downloaded.
	ServeUnknownFileTypes = true,
});

Some possible file content types

FileExtensionContentTypeProvider provider = new FileExtensionContentTypeProvider(new Dictionary<string, string>(StringComparer.OrdinalIgnoreCase) 
{
	{ ".323", "text/h323" },
	{ ".3g2", "video/3gpp2" },
	{ ".3gp2", "video/3gpp2" },
	{ ".3gp", "video/3gpp" },
	{ ".3gpp", "video/3gpp" },
	{ ".aac", "audio/aac" },
	{ ".aaf", "application/octet-stream" },
	{ ".aca", "application/octet-stream" },
	{ ".accdb", "application/msaccess" },
	{ ".accde", "application/msaccess" },
	{ ".accdt", "application/msaccess" },
	{ ".acx", "application/internet-property-stream" },
	{ ".adt", "audio/vnd.dlna.adts" },
	{ ".adts", "audio/vnd.dlna.adts" },
	{ ".afm", "application/octet-stream" },
	{ ".ai", "application/postscript" },
	{ ".aif", "audio/x-aiff" },
	{ ".aifc", "audio/aiff" },
	{ ".aiff", "audio/aiff" },
	{ ".application", "application/x-ms-application" },
	{ ".art", "image/x-jg" },
	{ ".asd", "application/octet-stream" },
	{ ".asf", "video/x-ms-asf" },
	{ ".asi", "application/octet-stream" },
	{ ".asm", "text/plain" },
	{ ".asr", "video/x-ms-asf" },
	{ ".asx", "video/x-ms-asf" },
	{ ".atom", "application/atom+xml" },
	{ ".au", "audio/basic" },
	{ ".avi", "video/x-msvideo" },
	{ ".axs", "application/olescript" },
	{ ".bas", "text/plain" },
	{ ".bcpio", "application/x-bcpio" },
	{ ".bin", "application/octet-stream" },
	{ ".bmp", "image/bmp" },
	{ ".c", "text/plain" },
	{ ".cab", "application/vnd.ms-cab-compressed" },
	{ ".calx", "application/vnd.ms-office.calx" },
	{ ".cat", "application/vnd.ms-pki.seccat" },
	{ ".cdf", "application/x-cdf" },
	{ ".chm", "application/octet-stream" },
	{ ".class", "application/x-java-applet" },
	{ ".clp", "application/x-msclip" },
	{ ".cmx", "image/x-cmx" },
	{ ".cnf", "text/plain" },
	{ ".cod", "image/cis-cod" },
	{ ".cpio", "application/x-cpio" },
	{ ".cpp", "text/plain" },
	{ ".crd", "application/x-mscardfile" },
	{ ".crl", "application/pkix-crl" },
	{ ".crt", "application/x-x509-ca-cert" },
	{ ".csh", "application/x-csh" },
	{ ".css", "text/css" },
	{ ".csv", "application/octet-stream" },
	{ ".cur", "application/octet-stream" },
	{ ".dcr", "application/x-director" },
	{ ".deploy", "application/octet-stream" },
	{ ".der", "application/x-x509-ca-cert" },
	{ ".dib", "image/bmp" },
	{ ".dir", "application/x-director" },
	{ ".disco", "text/xml" },
	{ ".dlm", "text/dlm" },
	{ ".doc", "application/msword" },
	{ ".docm", "application/vnd.ms-word.document.macroEnabled.12" },
	{ ".docx", "application/vnd.openxmlformats-officedocument.wordprocessingml.document" },
	{ ".dot", "application/msword" },
	{ ".dotm", "application/vnd.ms-word.template.macroEnabled.12" },
	{ ".dotx", "application/vnd.openxmlformats-officedocument.wordprocessingml.template" },
	{ ".dsp", "application/octet-stream" },
	{ ".dtd", "text/xml" },
	{ ".dvi", "application/x-dvi" },
	{ ".dvr-ms", "video/x-ms-dvr" },
	{ ".dwf", "drawing/x-dwf" },
	{ ".dwp", "application/octet-stream" },
	{ ".dxr", "application/x-director" },
	{ ".eml", "message/rfc822" },
	{ ".emz", "application/octet-stream" },
	{ ".eot", "application/vnd.ms-fontobject" },
	{ ".eps", "application/postscript" },
	{ ".etx", "text/x-setext" },
	{ ".evy", "application/envoy" },
	{ ".fdf", "application/vnd.fdf" },
	{ ".fif", "application/fractals" },
	{ ".fla", "application/octet-stream" },
	{ ".flr", "x-world/x-vrml" },
	{ ".flv", "video/x-flv" },
	{ ".gif", "image/gif" },
	{ ".gtar", "application/x-gtar" },
	{ ".gz", "application/x-gzip" },
	{ ".h", "text/plain" },
	{ ".hdf", "application/x-hdf" },
	{ ".hdml", "text/x-hdml" },
	{ ".hhc", "application/x-oleobject" },
	{ ".hhk", "application/octet-stream" },
	{ ".hhp", "application/octet-stream" },
	{ ".hlp", "application/winhlp" },
	{ ".hqx", "application/mac-binhex40" },
	{ ".hta", "application/hta" },
	{ ".htc", "text/x-component" },
	{ ".htm", "text/html" },
	{ ".html", "text/html" },
	{ ".htt", "text/webviewhtml" },
	{ ".hxt", "text/html" },
	{ ".ical", "text/calendar" },
	{ ".icalendar", "text/calendar" },
	{ ".ico", "image/x-icon" },
	{ ".ics", "text/calendar" },
	{ ".ief", "image/ief" },
	{ ".ifb", "text/calendar" },
	{ ".iii", "application/x-iphone" },
	{ ".inf", "application/octet-stream" },
	{ ".ins", "application/x-internet-signup" },
	{ ".isp", "application/x-internet-signup" },
	{ ".IVF", "video/x-ivf" },
	{ ".jar", "application/java-archive" },
	{ ".java", "application/octet-stream" },
	{ ".jck", "application/liquidmotion" },
	{ ".jcz", "application/liquidmotion" },
	{ ".jfif", "image/pjpeg" },
	{ ".jpb", "application/octet-stream" },
	{ ".jpe", "image/jpeg" },
	{ ".jpeg", "image/jpeg" },
	{ ".jpg", "image/jpeg" },
	{ ".js", "application/javascript" },
	{ ".jsx", "text/jscript" },
	{ ".latex", "application/x-latex" },
	{ ".lit", "application/x-ms-reader" },
	{ ".lpk", "application/octet-stream" },
	{ ".lsf", "video/x-la-asf" },
	{ ".lsx", "video/x-la-asf" },
	{ ".lzh", "application/octet-stream" },
	{ ".m13", "application/x-msmediaview" },
	{ ".m14", "application/x-msmediaview" },
	{ ".m1v", "video/mpeg" },
	{ ".m2ts", "video/vnd.dlna.mpeg-tts" },
	{ ".m3u", "audio/x-mpegurl" },
	{ ".m4a", "audio/mp4" },
	{ ".m4v", "video/mp4" },
	{ ".man", "application/x-troff-man" },
	{ ".manifest", "application/x-ms-manifest" },
	{ ".map", "text/plain" },
	{ ".mdb", "application/x-msaccess" },
	{ ".mdp", "application/octet-stream" },
	{ ".me", "application/x-troff-me" },
	{ ".mht", "message/rfc822" },
	{ ".mhtml", "message/rfc822" },
	{ ".mid", "audio/mid" },
	{ ".midi", "audio/mid" },
	{ ".mix", "application/octet-stream" },
	{ ".mmf", "application/x-smaf" },
	{ ".mno", "text/xml" },
	{ ".mny", "application/x-msmoney" },
	{ ".mov", "video/quicktime" },
	{ ".movie", "video/x-sgi-movie" },
	{ ".mp2", "video/mpeg" },
	{ ".mp3", "audio/mpeg" },
	{ ".mp4", "video/mp4" },
	{ ".mp4v", "video/mp4" },
	{ ".mpa", "video/mpeg" },
	{ ".mpe", "video/mpeg" },
	{ ".mpeg", "video/mpeg" },
	{ ".mpg", "video/mpeg" },
	{ ".mpp", "application/vnd.ms-project" },
	{ ".mpv2", "video/mpeg" },
	{ ".ms", "application/x-troff-ms" },
	{ ".msi", "application/octet-stream" },
	{ ".mso", "application/octet-stream" },
	{ ".mvb", "application/x-msmediaview" },
	{ ".mvc", "application/x-miva-compiled" },
	{ ".nc", "application/x-netcdf" },
	{ ".nsc", "video/x-ms-asf" },
	{ ".nws", "message/rfc822" },
	{ ".ocx", "application/octet-stream" },
	{ ".oda", "application/oda" },
	{ ".odc", "text/x-ms-odc" },
	{ ".ods", "application/oleobject" },
	{ ".oga", "audio/ogg" },
	{ ".ogg", "video/ogg" },
	{ ".ogv", "video/ogg" },
	{ ".ogx", "application/ogg" },
	{ ".one", "application/onenote" },
	{ ".onea", "application/onenote" },
	{ ".onetoc", "application/onenote" },
	{ ".onetoc2", "application/onenote" },
	{ ".onetmp", "application/onenote" },
	{ ".onepkg", "application/onenote" },
	{ ".osdx", "application/opensearchdescription+xml" },
	{ ".otf", "font/otf" },
	{ ".p10", "application/pkcs10" },
	{ ".p12", "application/x-pkcs12" },
	{ ".p7b", "application/x-pkcs7-certificates" },
	{ ".p7c", "application/pkcs7-mime" },
	{ ".p7m", "application/pkcs7-mime" },
	{ ".p7r", "application/x-pkcs7-certreqresp" },
	{ ".p7s", "application/pkcs7-signature" },
	{ ".pbm", "image/x-portable-bitmap" },
	{ ".pcx", "application/octet-stream" },
	{ ".pcz", "application/octet-stream" },
	{ ".pdf", "application/pdf" },
	{ ".pfb", "application/octet-stream" },
	{ ".pfm", "application/octet-stream" },
	{ ".pfx", "application/x-pkcs12" },
	{ ".pgm", "image/x-portable-graymap" },
	{ ".pko", "application/vnd.ms-pki.pko" },
	{ ".pma", "application/x-perfmon" },
	{ ".pmc", "application/x-perfmon" },
	{ ".pml", "application/x-perfmon" },
	{ ".pmr", "application/x-perfmon" },
	{ ".pmw", "application/x-perfmon" },
	{ ".png", "image/png" },
	{ ".pnm", "image/x-portable-anymap" },
	{ ".pnz", "image/png" },
	{ ".pot", "application/vnd.ms-powerpoint" },
	{ ".potm", "application/vnd.ms-powerpoint.template.macroEnabled.12" },
	{ ".potx", "application/vnd.openxmlformats-officedocument.presentationml.template" },
	{ ".ppam", "application/vnd.ms-powerpoint.addin.macroEnabled.12" },
	{ ".ppm", "image/x-portable-pixmap" },
	{ ".pps", "application/vnd.ms-powerpoint" },
	{ ".ppsm", "application/vnd.ms-powerpoint.slideshow.macroEnabled.12" },
	{ ".ppsx", "application/vnd.openxmlformats-officedocument.presentationml.slideshow" },
	{ ".ppt", "application/vnd.ms-powerpoint" },
	{ ".pptm", "application/vnd.ms-powerpoint.presentation.macroEnabled.12" },
	{ ".pptx", "application/vnd.openxmlformats-officedocument.presentationml.presentation" },
	{ ".prf", "application/pics-rules" },
	{ ".prm", "application/octet-stream" },
	{ ".prx", "application/octet-stream" },
	{ ".ps", "application/postscript" },
	{ ".psd", "application/octet-stream" },
	{ ".psm", "application/octet-stream" },
	{ ".psp", "application/octet-stream" },
	{ ".pub", "application/x-mspublisher" },
	{ ".qt", "video/quicktime" },
	{ ".qtl", "application/x-quicktimeplayer" },
	{ ".qxd", "application/octet-stream" },
	{ ".ra", "audio/x-pn-realaudio" },
	{ ".ram", "audio/x-pn-realaudio" },
	{ ".rar", "application/octet-stream" },
	{ ".ras", "image/x-cmu-raster" },
	{ ".rf", "image/vnd.rn-realflash" },
	{ ".rgb", "image/x-rgb" },
	{ ".rm", "application/vnd.rn-realmedia" },
	{ ".rmi", "audio/mid" },
	{ ".roff", "application/x-troff" },
	{ ".rpm", "audio/x-pn-realaudio-plugin" },
	{ ".rtf", "application/rtf" },
	{ ".rtx", "text/richtext" },
	{ ".scd", "application/x-msschedule" },
	{ ".sct", "text/scriptlet" },
	{ ".sea", "application/octet-stream" },
	{ ".setpay", "application/set-payment-initiation" },
	{ ".setreg", "application/set-registration-initiation" },
	{ ".sgml", "text/sgml" },
	{ ".sh", "application/x-sh" },
	{ ".shar", "application/x-shar" },
	{ ".sit", "application/x-stuffit" },
	{ ".sldm", "application/vnd.ms-powerpoint.slide.macroEnabled.12" },
	{ ".sldx", "application/vnd.openxmlformats-officedocument.presentationml.slide" },
	{ ".smd", "audio/x-smd" },
	{ ".smi", "application/octet-stream" },
	{ ".smx", "audio/x-smd" },
	{ ".smz", "audio/x-smd" },
	{ ".snd", "audio/basic" },
	{ ".snp", "application/octet-stream" },
	{ ".spc", "application/x-pkcs7-certificates" },
	{ ".spl", "application/futuresplash" },
	{ ".spx", "audio/ogg" },
	{ ".src", "application/x-wais-source" },
	{ ".ssm", "application/streamingmedia" },
	{ ".sst", "application/vnd.ms-pki.certstore" },
	{ ".stl", "application/vnd.ms-pki.stl" },
	{ ".sv4cpio", "application/x-sv4cpio" },
	{ ".sv4crc", "application/x-sv4crc" },
	{ ".svg", "image/svg+xml" },
	{ ".svgz", "image/svg+xml" },
	{ ".swf", "application/x-shockwave-flash" },
	{ ".t", "application/x-troff" },
	{ ".tar", "application/x-tar" },
	{ ".tcl", "application/x-tcl" },
	{ ".tex", "application/x-tex" },
	{ ".texi", "application/x-texinfo" },
	{ ".texinfo", "application/x-texinfo" },
	{ ".tgz", "application/x-compressed" },
	{ ".thmx", "application/vnd.ms-officetheme" },
	{ ".thn", "application/octet-stream" },
	{ ".tif", "image/tiff" },
	{ ".tiff", "image/tiff" },
	{ ".toc", "application/octet-stream" },
	{ ".tr", "application/x-troff" },
	{ ".trm", "application/x-msterminal" },
	{ ".ts", "video/vnd.dlna.mpeg-tts" },
	{ ".tsv", "text/tab-separated-values" },
	{ ".ttf", "application/octet-stream" },
	{ ".tts", "video/vnd.dlna.mpeg-tts" },
	{ ".txt", "text/plain" },
	{ ".u32", "application/octet-stream" },
	{ ".uls", "text/iuls" },
	{ ".ustar", "application/x-ustar" },
	{ ".vbs", "text/vbscript" },
	{ ".vcf", "text/x-vcard" },
	{ ".vcs", "text/plain" },
	{ ".vdx", "application/vnd.ms-visio.viewer" },
	{ ".vml", "text/xml" },
	{ ".vsd", "application/vnd.visio" },
	{ ".vss", "application/vnd.visio" },
	{ ".vst", "application/vnd.visio" },
	{ ".vsto", "application/x-ms-vsto" },
	{ ".vsw", "application/vnd.visio" },
	{ ".vsx", "application/vnd.visio" },
	{ ".vtx", "application/vnd.visio" },
	{ ".wav", "audio/wav" },
	{ ".wax", "audio/x-ms-wax" },
	{ ".wbmp", "image/vnd.wap.wbmp" },
	{ ".wcm", "application/vnd.ms-works" },
	{ ".wdb", "application/vnd.ms-works" },
	{ ".webm", "video/webm" },
	{ ".wks", "application/vnd.ms-works" },
	{ ".wm", "video/x-ms-wm" },
	{ ".wma", "audio/x-ms-wma" },
	{ ".wmd", "application/x-ms-wmd" },
	{ ".wmf", "application/x-msmetafile" },
	{ ".wml", "text/vnd.wap.wml" },
	{ ".wmlc", "application/vnd.wap.wmlc" },
	{ ".wmls", "text/vnd.wap.wmlscript" },
	{ ".wmlsc", "application/vnd.wap.wmlscriptc" },
	{ ".wmp", "video/x-ms-wmp" },
	{ ".wmv", "video/x-ms-wmv" },
	{ ".wmx", "video/x-ms-wmx" },
	{ ".wmz", "application/x-ms-wmz" },
	{ ".woff", "application/font-woff" },
	{ ".wps", "application/vnd.ms-works" },
	{ ".wri", "application/x-mswrite" },
	{ ".wrl", "x-world/x-vrml" },
	{ ".wrz", "x-world/x-vrml" },
	{ ".wsdl", "text/xml" },
	{ ".wtv", "video/x-ms-wtv" },
	{ ".wvx", "video/x-ms-wvx" },
	{ ".x", "application/directx" },
	{ ".xaf", "x-world/x-vrml" },
	{ ".xaml", "application/xaml+xml" },
	{ ".xap", "application/x-silverlight-app" },
	{ ".xbap", "application/x-ms-xbap" },
	{ ".xbm", "image/x-xbitmap" },
	{ ".xdr", "text/plain" },
	{ ".xht", "application/xhtml+xml" },
	{ ".xhtml", "application/xhtml+xml" },
	{ ".xla", "application/vnd.ms-excel" },
	{ ".xlam", "application/vnd.ms-excel.addin.macroEnabled.12" },
	{ ".xlc", "application/vnd.ms-excel" },
	{ ".xlm", "application/vnd.ms-excel" },
	{ ".xls", "application/vnd.ms-excel" },
	{ ".xlsb", "application/vnd.ms-excel.sheet.binary.macroEnabled.12" },
	{ ".xlsm", "application/vnd.ms-excel.sheet.macroEnabled.12" },
	{ ".xlsx", "application/vnd.openxmlformats-officedocument.spreadsheetml.sheet" },
	{ ".xlt", "application/vnd.ms-excel" },
	{ ".xltm", "application/vnd.ms-excel.template.macroEnabled.12" },
	{ ".xltx", "application/vnd.openxmlformats-officedocument.spreadsheetml.template" },
	{ ".xlw", "application/vnd.ms-excel" },
	{ ".xml", "text/xml" },
	{ ".xof", "x-world/x-vrml" },
	{ ".xpm", "image/x-xpixmap" },
	{ ".xps", "application/vnd.ms-xpsdocument" },
	{ ".xsd", "text/xml" },
	{ ".xsf", "text/xml" },
	{ ".xsl", "text/xml" },
	{ ".xslt", "text/xml" },
	{ ".xsn", "application/octet-stream" },
	{ ".xtp", "application/octet-stream" },
	{ ".xwd", "image/x-xwindowdump" },
	{ ".z", "application/x-compress" },
	{ ".zip", "application/x-zip-compressed" },
});