Sodium Hydroxide → N-(4-fluorophenyl)-1-(methylsulfonyl)-2-(1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridin-6-amine

HRID 2205957Notes

Reaction equation

[OH-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:16]=[CH:15][C:14]3[CH:17]=[C:18]([C:24]4[CH:25]=[N:26][N:27](C(OC(C)(C)C)=O)[CH:28]=4)[N:19]([S:20]([CH3:23])(=[O:22])=[O:21])[C:13]=3[CH:12]=2)=[CH:6][CH:5]=1.ClC1N=CC2C=C(C3C=NN(C(OC(C)(C)C)=O)C=3)N(S(C)(=O)=O)C=2C=1>CCO>[F:3][C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11]2[N:16]=[CH:15][C:14]3[CH:17]=[C:18]([C:24]4[CH:25]=[N:26][NH:27][CH:28]=4)[N:19]([S:20]([CH3:23])(=[O:21])=[O:22])[C:13]=3[CH:12]=2)=[CH:8][CH:9]=1

Participants

Conditions

Temperature: 40 °C

Procedure

Aqueous sodium hydroxide (127 μL, 1 M, 0.127 mmol) was added to a solution of tert-butyl 4-(6-(4-fluorophenylamino)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate (Preparation 53, 20 mg, 0.042 mmol) (mixed with some tert-butyl 4-(6-chloro-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate) in EtOH (339 μL). The reaction mixture was stirred for 4 hours at 40° C. The reaction mixture was filtered on SCX-2 column and was then purified using preparative TLC eluting with DCM/MeOH, 95/5 to afford the title compound as a white solid (7 mg, 20%). 1H NMR (500 MHz, CD3OD): δ 3.02 (s, 3H), 6.73 (d, J=0.8 Hz, 1H), 7.00-7.07 (m, 2H), 7.45-7.49 (m, 2H), 7.51 (t, J=0.8 Hz, 1H), 7.90 (br s, 2H), 8.40 (d, J=0.8 Hz, 1H). ESI-HRMS Found 372.0936, calculated for C17H15FN5O2S [M+H]+: 372.0925. MPS1 IC50 (uM): 6.43

Workup

filtrationThe reaction mixture was filtered on SCX-2 column
customwas then purified
washeluting with DCM/MeOH, 95/5

Sources & evidence

ORD record: ord-06dc2e19b43c4d11856f1bc8b6ff40df
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371319B2

Reaction notes

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