1,2-Dibromoethane → N-[1-(2-bromoethyl)-3-[5-chloro-2-(difluoromethoxy) phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 529780Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH:26]([F:28])[F:27])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][NH:10][N:9]=2)[CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[Br:35][CH2:36][CH2:37]Br>O1CCCC1>[Br:35][CH2:36][CH2:37][N:10]1[CH:11]=[C:12]([NH:13][C:14]([C:16]2[CH:17]=[N:18][N:19]3[CH:24]=[CH:23][CH:22]=[N:21][C:20]=23)=[O:15])[C:8]([C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[O:25][CH:26]([F:28])[F:27])=[N:9]1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (3.00 g, 7.41 mmol), Cs2CO3 (9.90 g, 30.38 mmol), tetrahydrofuran (90 mL), 1,2-dibromoethane (7.00 g, 37.26 mmol) was stirred at 70° C. for 3 hours in an oil bath. The mixture was allowed to cool to ambient temperature then concentrated under reduced pressure. The residue was purified by flash chromatography on silica eluting with ethyl acetate/petroleum ether (1:1) to afford N-[1-(2-bromoethyl)-3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]-pyrimidine-3-carboxamide as a off-white solid (2.2 g, 58%). TLC: Rf=0.6; ethyl acetate/petroleum ether=1:1; LCMS (Method 14) [M+H]+=513.2, RT=1.03 min.

Workup

temperatureto cool to ambient temperature
concentrationthen concentrated under reduced pressure
customThe residue was purified by flash chromatography on silica eluting with ethyl acetate/petroleum ether (1:1)

Sources & evidence

ORD record: ord-5c94be499ecf402bbab6201a59dc2303
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346815B2

Reaction notes

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