1,8-Diazabicyclo(5.4.0)undec-7-ene → N-(5-fluoropyridin-2-yl)-2-(1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridin-6-amine

HRID 2205959Notes

Reaction equation

C1CCN2C(=NCCC2)CC1.[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:34]=[N:35][N:36](C(OC(C)(C)C)=O)[CH:37]=4)[N:28](S(C)(=O)=O)[C:22]=3[CH:21]=2)=[N:17][CH:18]=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)=[N:17][CH:18]=1

Participants

Conditions

Temperature: 100 °C

Procedure

DBU (10.8 μL, 0.072 mmol) was added to a solution of tert-butyl 4-(6-(5-fluoropyridin-2-ylamino)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate (Preparation 54, 17 mg, 0.036 mmol) in DMF (240 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 5% MeOH/aq NH3 10/1 in DCM to afford the title compound as a white solid (7 mg, 24%). 1H NMR (500 MHz, CD3OD): δ 6.66 (d, J=0.9 Hz, 1H), 7.18-7.21 (m, 1H), 7.46-7.50 (m, 1H), 7.71 (s, 1H), 8.03 (br s, 2H), 8.07-8.09 (m, 1H), 8.42 (d, J=0.9 Hz, 1H). ESI-HRMS Found 295.1103, calculated for C15H12FN6 [M+H]+: 295.1102. MPS1 IC50 (uM): 0.1586

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 5% MeOH/aq NH3 10/1 in DCM

Sources & evidence

ORD record: ord-d65820c85c2b4f0fa7a9e3d64348684b
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371319B2

Reaction notes

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