Acetaldehyde → 3-[5-chloro-2-(1,4-diethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-thiophene-2-carboxylic acid methylamide

HRID 1688137Notes

Reaction equation

[CH:1](=O)[CH3:2].[CH3:4][NH:5][C:6]([C:8]1[S:9][CH:10]=[CH:11][C:12]=1[NH:13][C:14]1[C:19]([Cl:20])=[CH:18][N:17]=[C:16]([NH:21][C:22]2[CH:23]=[CH:24][C:25]3[CH2:31][NH:30][CH2:29][C:28](=[O:32])[N:27]([CH2:33][CH3:34])[C:26]=3[CH:35]=2)[N:15]=1)=[O:7].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.ClCCCl>[CH3:4][NH:5][C:6]([C:8]1[S:9][CH:10]=[CH:11][C:12]=1[NH:13][C:14]1[C:19]([Cl:20])=[CH:18][N:17]=[C:16]([NH:21][C:22]2[CH:23]=[CH:24][C:25]3[CH2:31][N:30]([CH2:1][CH3:2])[CH2:29][C:28](=[O:32])[N:27]([CH2:33][CH3:34])[C:26]=3[CH:35]=2)[N:15]=1)=[O:7]

Participants

Conditions

Temperature: 0 °C

Procedure

Acetaldehyde (20 mg, 0.45 mmol) was added to a solution of 3-[5-chloro-2-(1-ethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-thiophene-2-carboxylic acid methylamide (42.5 mg, 0.09 mmol) in THF:DCE (1:2) at 0° C. After 15 minutes, 100 mg of sodium triacetoxyborohydride was added and the mixture was stirred for 2 hours at 0° C. and 1 hour at room temperature. Evaporation and chromatography on preparative TLC with methylene chloride and methanol (100:7) gave 31 mg of 3-[5-chloro-2-(1,4-diethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-thiophene-2-carboxylic acid methylamide (50%): 1H NMR (300 MHz, CD3OD) δ 8.42 (d, 1H), 8.07 (s, 1H), 7.83 (s, 1H), 7.44 (d, 1H), 7.42 (s, 1H), 7.27 (d, 1H), 3.9 (q, 2H), 3.64 (s, 2H), 3.22 (s, 2H), 2.87 (s, 3H), 2.75 (q, 2H), 2.05 (s, 3H), 1.18 (m, 6H); MS (m/e): 500.4 (M+1).

Workup

customEvaporation and chromatography on preparative TLC with methylene chloride and methanol (100:7)

Sources & evidence

ORD record: ord-9bbc3f6b3ecf4c67976d847d71ef2334
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148391B2

Reaction notes

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