Cyclopropanecarboxylic acid → N-(2-(4-(3-((4-(difluoromethyl)pyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)ethyl)cyclopropanecarboxamide

HRID 595314Notes

Reaction equation

HRID 595314 reaction equation
C(N(CC)C(C)C)(C)C.[CH:10]1([C:13]([OH:15])=O)[CH2:12][CH2:11]1.[Cl-].ClC1N(C)CC[NH+]1C.Cl.[NH2:26][CH2:27][CH2:28][N:29]1[CH:33]=[C:32]([C:34]2[CH:35]=[C:36]([NH:41][C:42]3[N:47]=[C:46]([CH:48]([F:50])[F:49])[CH:45]=[CH:44][N:43]=3)[CH:37]=[C:38]([CH3:40])[CH:39]=2)[CH:31]=[N:30]1>ClCCl>[F:50][CH:48]([F:49])[C:46]1[CH:45]=[CH:44][N:43]=[C:42]([NH:41][C:36]2[CH:35]=[C:34]([C:32]3[CH:31]=[N:30][N:29]([CH2:28][CH2:27][NH:26][C:13]([CH:10]4[CH2:12][CH2:11]4)=[O:15])[CH:33]=3)[CH:39]=[C:38]([CH3:40])[CH:37]=2)[N:47]=1

Participants

6

Reactant 4

HCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 109867151H-Imidazolium, 2-chloro-4,5-dihydro-1,3-dimethyl-, chlorideHCID 118208517N-(3-(1-(2-amino ethyl)-1H-pyrazol-4-yl)-5-methylphenyl)-4-(difluoromethyl)pyrimidin-2-amine hydrochloride

Product 1

HCID 118208660N-(2-(4-(3-((4-(difluoromethyl)pyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)ethyl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dichloromethane (1 mL) and N,N-diisopropylethylamine (0.087 mL, 0.50 mmol) were added to a vial containing cyclopropanecarboxylic acid (17.2 mg, 0.2 mmol) and 2-chloro-1,3-dimethylimidazolinium chloride (0.025 g, 0.15 mmol). The reaction mixture was stirred for 10 minutes and N-(3-(1-(2-amino ethyl)-1H-pyrazol-4-yl)-5-methylphenyl)-4-(difluoromethyl)pyrimidin-2-amine hydrochloride (38 mg, 0.10 mmol) was added. The reaction mixture was stirred for two hours and then concentrated under reduced pressure. The residue was purified by reverse phase chromatography (acetonitrile/water with 0.1% TFA modifier) to afford N-(2-(4-(3-((4-(difluoromethyl)pyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)ethyl)cyclopropanecarboxamide. MS ESI calc'd. for C21H23F2N6O [M+H]+ 413. found 413. 1H NMR (600 MHz, DMSO): δ 9.78 (s, 1H), 8.64 (d, J=4.9 Hz, 1H), 8.19 (s, 1H), 7.96 (s, 1H), 7.77 (s, 1H), 7.76 (s, 1H), 7.29 (s, 1H), 7.01 (d, J=4.9 Hz, 1H), 7.00 (s, 1H), 6.80 (t, J=54.5 Hz, 1H), 4.13 (t, J=6.2 Hz, 2H), 3.44 (q, J=6.0 Hz, 2H), 2.25 (s, 3H), 1.47-1.45 (m, 1H), 0.61-0.59 (m, 4H).

Workup

  1. stirringThe reaction mixture was stirred for two hours
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by reverse phase chromatography (acetonitrile/water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-632fec0eec8f40d7b1b40588b5b4bc70
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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