2-Pyridinemethanamine,5-fluoro-(9CI) synthesis
- Product Name:2-Pyridinemethanamine,5-fluoro-(9CI)
- CAS Number:561297-96-9
- Molecular formula:C6H7FN2
- Molecular Weight:126.13
327056-62-2
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561297-96-9
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Yield: 44%
Reaction Conditions:
with ammonia;hydrogen;nickel in ethanol at 70; under 25858.1 Torr; for 16 h;
Steps:
85
Preparation 85; 2-Aminomethyl-5-fluoropyridine (dihydrochloride); Combine a mixture of 2-cyano-5-fluoropyridine (63.2 g, 0.52 mol), 22.5 g of Raney nickel, and ethanol (1.5 L) saturated with ammonia and hydrogenate at 500 p. s. i. and 70 ° C for 16 h. Chromatograph the dark purple liquid over flash silica gel (methylene chloride/methanol/ammonia hydroxide-95: 4.5 : 0.5) to give, after concentration at 25-30 ° C, a yellow liquid of the pure desired free base, 25.0 g (44%); 'H NMR (DMSO-d6) 8 8.43 (d, J= 2.9 Hz, 1H), 7.66 (m, 1H), 7.50 (m, 1H), 3.77 (s, 2H), 2.10 (br, 2H); MS (ESI) m/z 127 (m+H). Add to a solution of the free base (20.0 g, 159.0 mmol) in 150 ml of 1,4-dioxane, 4N HC1 in dioxane (150 mL, 3.8 eq. ) and a white solid separates immediately. Dilute the solid with ethyl ether (300 mL) and filter. Dry the product at 20 mm Hg, 60 ° C, to give the pure dihydrochloride title compound, 30.0 g (95%) ; lH NMR (DMSO-d6) 6 8.61 (d, J= 2.9 Hz, 1H), 8.50 (brs, 3H), 7.82 (m, 1H), 7.62 (m, 1H), 7.50 (br, 1H), 4.18 (m, 2H); MS (ESI) m/z 127 (rn+H, free base).
References:
ELI LILLY AND COMPANY WO2005/66126, 2005, A1 Location in patent:Page/Page column 76