Dimethylformamide → HCID 67459701, compound

HRID 1853057Notes

Reaction equation

Cl.[CH3:2][N:3]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]3[CH:18]=[CH:17][N:16]([C:19]4([CH2:23][C:24]#[N:25])[CH2:22][NH:21][CH2:20]4)[N:15]=3)[N:11]3[CH:26]=[CH:27][N:28]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1.CN(C=O)C.C(N(C(C)C)CC)(C)C.FC(F)(F)S(O[CH2:49][C:50]([F:53])([F:52])[F:51])(=O)=O>>[CH3:2][N:3]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]3[CH:18]=[CH:17][N:16]([C:19]4([CH2:23][C:24]#[N:25])[CH2:22][N:21]([CH2:49][C:50]([F:53])([F:52])[F:51])[CH2:20]4)[N:15]=3)[N:11]3[CH:26]=[CH:27][N:28]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1

Participants

Reactant 4

HCID 6228Dimethylformamide

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonate2×

HCID 81531Diisopropylethylamine

HCID 67458429HCID 67458429, compound

Product 1

HCID 67459701HCID 67459701, compoundYield 72.3%

Procedure

2-(3-(3-(7-(1-Methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile hydrochloride (Example 130; 13.0 mg, 0.0301 mmol) was suspended in DMF (301 μL, 0.0301 mmol) and treated with diisopropylethylamine (31.4 μL, 0.180 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (9.07 mg, 0.0391 mmol). The reaction mixture was stirred at ambient temperature for 15 hours. Another portion of 2,2,2-trifluoroethyl trifluoromethanesulfonate (2.0 mg, 0.87 mmol) was added and stirred for another 24 hours. The reaction mixture was then purified by reverse phase HPLC using 0-100% acetonitrile/water gradient, followed by preparative TLC using 10% MeOH/EtOAc to afford 2-(3-(3-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(2,2,2-trifluoroethyl)azetidin-3-yl)acetonitrile (9.6 mg, 72% yield). MS (apci) m/z=442.3 (M+H).

Workup

stirringstirred for another 24 hours
customThe reaction mixture was then purified by reverse phase

Sources & evidence

ORD record: ord-1c965d32ecb94f3cae9e405d30fec374
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962596B2

Reaction notes

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