Water → 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid benzylamide

HRID 570494Notes

Reaction equation

[CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Al](C)C.C[O:14][C:15]([C:17]1[S:18][CH:19]=[CH:20][C:21]=1[NH:22][C:23]1[C:24]2[CH:31]=[CH:30][NH:29][C:25]=2[N:26]=[CH:27][N:28]=1)=O.O>C1(C)C=CC=CC=1.CO>[CH2:1]([NH:8][C:15]([C:17]1[S:18][CH:19]=[CH:20][C:21]=1[NH:22][C:23]1[C:24]2[CH:31]=[CH:30][NH:29][C:25]=2[N:26]=[CH:27][N:28]=1)=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 105 °C

Procedure

To a solution of benzylamine (99 μl; 98 mg; 0.91 mmol) in anhydrous toluene (3 mL) placed in a sealed tube under nitrogen was added a solution of trimethylaluminum (365 μl; 2 M; 0.73 mmol) in toluene. The colorless solution was stirred at 25° C. for 1 h, before 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid methyl ester (50 mg; 0.18 mmol) was added and the resulting yellow suspension was heated to 105° C. overnight. The reaction mixture was allowed to cool down before water (0.1 mL) was added. The resulting blue suspension was stirred at 25° C. for 2 h, diluted with methanol and purified by chromatography on a SP1 Biotage system, using dichloromethane and methanol as eluents to afford 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-thiophene-2-carboxylic acid benzylamide (26 mg, 39%) as a gray solid (HPLC: 95%, RT: 6.04 min). 1H NMR (DMSO-d6) 11.96 (br s, 1H), 11.39 (s, 1H), 8.82 (t, J=5.9 Hz, 1H), 8.50 (d, J=5.1 Hz, 1H), 8.38 (s, 1H), 7.79 (d, J=5.5 Hz, 1H), 7.36-7.33 (m, 5H), 7.27-7.22 (m, 1H), 6.43 (dd, J=3.3, 1.8 Hz, 1H), 4.50 (d, J=5.9 Hz, 2H); MS (m/z) 350 [M+H]+.

Workup

additionwas added
additionwas added
custompurified by chromatography on a SP1 Biotage system

Sources & evidence

ORD record: ord-22b63ff50df645a2af836ae6cd334a64
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09023847B2

Reaction notes

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