Diisopropylethylamine → 5-Chloro-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-(1-(5-fluoropyridin-2-yl)ethyl)pyrimidine-2,4-diamine

HRID 1641383Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)[C:5]([Cl:17])=[CH:4][N:3]=1.[F:18][C:19]1[CH:20]=[CH:21][C:22]([CH:25]([NH2:27])[CH3:26])=[N:23][CH:24]=1.CCN(C(C)C)C(C)C>CCCCO>[Cl:17][C:5]1[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)=[N:7][C:2]([NH:27][CH:25]([C:22]2[CH:21]=[CH:20][C:19]([F:18])=[CH:24][N:23]=2)[CH3:26])=[N:3][CH:4]=1

Participants

Conditions

Temperature: 185 °C

Procedure

A mixture of 2,5-dichloro-4-(5-cyclopropyl-1H-pyrazole-3-ylamino)pyrimidine (Method 7; 0.14 g, 0.518 mmol), 1-(5-fluoropyridin-2-yl)ethanamine (Method 4; 0.091 g, 0.648 mmol), and DIEA (0.11 ml, 0.648 mmol) in n-BuOH (2 ml) was heated in a sealed tube at 185° C. for 18 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane-EtOAc=1:2) to give the title compound as a white solid (0.070 g, 36%). 1H NMR (400 MHz) 12.51 and 12.09 (s, 1H), 9.65 (s, 1H), 8.48 (s, 1H), 8.38 (s, 1H), 8.02 and 7.93 (b, 1H), 7.64 (m, 1H), 7.41 (m, 1H), 5.93 and 5.80 (b, 1H), 5.06 (m, 1H), 1.83 (m, 1H), 1.45 (d, J=6.8 Hz, 3H), 0.95 (m, 1H), 0.84 (m, 1H), 0.74 (m, 1H), 0.63 (m, 1H). MS: Calcd.: 373. Found: [M+H]+374.

Workup

customThe solvent was removed under reduced pressure
customthe residue was purified by column chromatography (hexane-EtOAc=1:2)

Sources & evidence

ORD record: ord-644b5f4881ea48eea46467970baa5f5c
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08114989B2

Reaction notes

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