Potassium Carbonate → (E)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(3-methoxyprop-1-enyl)-2-phenylpyrimidin-4-amine

HRID 1484868Notes

Reaction equation

[CH:1]1([C:4]2[N:8](C(OC(C)(C)C)=O)[N:7]=[C:6]([NH:16][C:17]3[C:22](I)=[CH:21][N:20]=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[N:18]=3)[CH:5]=2)[CH2:3][CH2:2]1.[CH3:30][O:31][CH2:32]/[CH:33]=[CH:34]/B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:16][C:17]3[C:22](/[CH:34]=[CH:33]/[CH2:32][O:31][CH3:30])=[CH:21][N:20]=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[N:18]=3)[CH:5]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of tert-butyl 5-cyclopropyl-3-(5-iodo-2-phenylpyrimidin-4-ylamino)-1H-pyrazole-1-carboxylate (318 mg, 0.63 mmol, 1.0 equiv.), (E)-2-(3-methoxyprop-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (500 mg, 2.53 mmol, 4.0 equiv.), PdCl2(dppf2)′CH2Cl2 (155 mg, 0.19 mmol, 0.3 equiv.) and K2CO3 (348 mg, 2.53 mmol, 4.0 equiv.) in dry DMF (40 mL) was heated to 90° C. under a nitrogen atmosphere and stirred for 2 hours. Then, the reaction mixture was cooled down to room temperature and concentrated in vacuum. The residue was purified by Prep-HPLC to give the title compound (E)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-(3-methoxyprop-1-enyl)-2-phenylpyrimidin-4-amine (Compound 39) (10 mg, 2%). LCMS: 348.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 0.72-0.78 (m, 2H), 0.96-0.98 (m, 2H), 1.94-2.02 (m, 1H), 3.30 (s, 3H), 4.06 (d, J=5.2 Hz, 2H), 6.33 (m, 1H), 6.46 (s, 1H), 7.02 (d, J=15.6 Hz, 1H), 7.48 (m, 3H), 8.29 (d, J=4.4 Hz, 2H), 8.53 (s, 1H), 9.26 (s, 1H), 12.15 (s, 1H).

Workup

temperatureThen, the reaction mixture was cooled down to room temperature
concentrationconcentrated in vacuum
customThe residue was purified by Prep-HPLC

Sources & evidence

ORD record: ord-44db9e69bef44f839d4b64da6c0cc339
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422271B2

Reaction notes

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