Triethylamine → 5-chloro-N2-(4-(1-((2,2-difluorocyclopropyl)methyl)piperidin-4-yl)-2-fluoro-5-methylphenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

HRID 536400Notes

Reaction equation

[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:11][C:10]=2[F:22])=[N:6][CH:7]=1.Br[CH2:31][CH:32]1[CH2:34][C:33]1([F:36])[F:35].C(N(CC)CC)C>CN(C=O)C>[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:17][CH2:18][N:19]([CH2:31][CH:32]4[CH2:34][C:33]4([F:36])[F:35])[CH2:20][CH2:21]3)=[CH:11][C:10]=2[F:22])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 5-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (40 mg, 0.096 mmol), 2-(bromomethyl)-1,1-difluorocyclopropane (32.8 mg, 0.19 mmol) and triethylamine (20.2 μL, 0.14 mmol) in 1 mL of DMF was heated at 150° C. in a microwave reactor for 30 min. The crude product was purified by RP-HPLC to afford 5-chloro-N2-(4-(1-((2,2-difluorocyclopropyl)methyl)piperidin-4-yl)-2-fluoro-5-methylphenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine; ESMS m/z 506.2 (M+H+).

Workup

customThe crude product was purified by RP-HPLC

Sources & evidence

ORD record: ord-a873f91180e7450aaa8bdeac8f143e85
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08859574B2

Reaction notes

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