1,8-Diazabicyclo(5.4.0)undec-7-ene → N-(4-fluorophenyl)-2-(1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridin-6-amine

HRID 2205958Notes

Reaction equation

C1CCN2C(=NCCC2)CC1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]2[N:25]=[CH:24][C:23]3[CH:26]=[C:27]([C:33]4[CH:34]=[N:35][NH:36][CH:37]=4)[N:28](S(C)(=O)=O)[C:22]=3[CH:21]=2)=[CH:15][CH:14]=1>CN(C=O)C.O>[F:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][C:20]2[N:25]=[CH:24][C:23]3[CH:26]=[C:27]([C:33]4[CH:37]=[N:36][NH:35][CH:34]=4)[NH:28][C:22]=3[CH:21]=2)=[CH:17][CH:18]=1

Participants

Conditions

Temperature: 100 °C

Procedure

DBU (2 μL, 0.016 mmol) was added to a solution of N-(4-fluorophenyl)-1-(methylsulfonyl)-2-(1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridin-6-amine (Example 187, 3 mg, 8.08 μmol) in DMF (54 μL). The reaction mixture was stirred for 1 hour at 50° C. and for 1 hour at 100° C. The reaction mixture was diluted with water and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was then purified using preparative TLC eluting with DCM/MeOH, 90/10 to afford the title compound as a brown solid (2 mg, 84%). 1H NMR (500 MHz, CD3OD): δ 6.60 (d, J=0.9 Hz), 6.85 (s, 1H), 6.99-7.06 (m, 2H), 7.26-7.32 (m, 2H), 8.00 (br s, 2H), 8.34 (s, 1H). ESI-HRMS Found 294.1158, calculated for C16H13FN5 [M+H]+: 294.1150. MPS1 IC50 (uM): 0.140

Workup

extractionthe aqueous layer was extracted with EtOAc
dry with materialThe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was then purified
washeluting with DCM/MeOH, 90/10

Sources & evidence

ORD record: ord-230b37244c20406ab9ee0e9a0bca7245
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371319B2

Reaction notes

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