Potassium Phosphate, Tribasic → Ethyl 4-amino-5-{4-[(tert-butoxycarbonyl)amino]-3-fluorophenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate

HRID 73658Notes

Reaction equation

[NH2:1][N:2]1[C:6]([C:7]#[N:8])=[C:5]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[C:11]([F:23])[CH:10]=2)[C:4]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:3]1.C(O)(=O)C.[CH:33](N)=[NH:34].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(O)C.O>[NH2:8][C:7]1[C:6]2=[C:5]([C:9]3[CH:14]=[CH:13][C:12]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[C:11]([F:23])[CH:10]=3)[C:4]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:3][N:2]2[N:1]=[CH:33][N:34]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of ethyl 1-amino-4-{4-[(tert-butoxycarbonyl)amino]-3-fluorophenyl}-5-cyano-1H-pyrrole-3-carboxylate (18.06 g, 46.5 mmol), formamidine acetate (48.41 g, 464.9 mmol) and finely ground potassium phosphate (19.74 g, 93.0 mmol) in ethanol (350 mL) was heated at 80° C. overnight. After 16 h, the reaction mixture was cooled to rt and diluted with 1.8 L water. The resulting precipitate was filtered thru a glass frit and washed with water. Drying in a vacuum oven provided the title compound as a gray solid (15.6 g, 80.8%) 1H-NMR (DMSO-d6) δ 9.11 (s, 1H), 8.13 (s, 1H), 7.93 (s, 1H), 7.72 (t, J=8 Hz, 1H), 7.26 (dd, J=12, 2 Hz, 1H), 7.12 (dd, J=8, 2 Hz, 1H), 4.07 (q, J=7 Hz, 2H), 1.47 (s, 9H), 1.09 (t, J=7 Hz, 3H); MS [M+H]+ 415.8=;. LCMS RT=3.05.

Workup

temperaturethe reaction mixture was cooled to rt
filtrationThe resulting precipitate was filtered thru a glass frit
washwashed with water
customDrying in a vacuum oven

Sources & evidence

ORD record: ord-c990c67ab660482cba7c472db1fa5110
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08829185B2

Reaction notes

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