Diisopropylethylamine → 5-chloro-N2-(1-(5-fluoropyrimidin-2-yl)ethyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

HRID 415402Notes

Reaction equation

[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:23]=[C:22](OC(C)C)[NH:21][N:20]=2)=[N:4][C:5]([NH:8][CH:9]([C:11]2[N:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)[CH3:10])=[N:6][CH:7]=1.[CH:28]1(C2NN=C(NC3C(F)=CN=C(N[C@H](C4N=CC(F)=CN=4)C)N=3)C=2)CC1.CCN(C(C)C)C(C)C>CCCCO>[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:23]=[C:22]([CH3:28])[NH:21][N:20]=2)=[N:4][C:5]([NH:8][CH:9]([C:11]2[N:12]=[CH:13][C:14]([F:17])=[CH:15][N:16]=2)[CH3:10])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 180 °C

Procedure

A mixture of rac-1-(5-fluoropyrimidin-2-yl)ethanamine hydrochloride (Method 1, 100 mg), 2,5-dichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (Method 9, 200 mg) and DIPEA (0.150 ml) in n-BuOH (2.5 ml) was charged into a microwave reaction vessel. The vessel was sealed and heated in microwave reactor at 180° C. for 6 hours. The solvent was removed under reduced pressure and the residue was purified by Gilson (10-50% MeCN/H2O, 15 min) to give 5-chloro-N2-[1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine as solid (55 mg). The tile compound was obtained after chiral purification using SFC conditions (Chiralpak AD-H, 20% i-PrOH/80% CO2/0.1% Dimethylethylamine). 1H NMR (300 MHz, DMSO-d6) δ 12.03 (s, 1H) 8.83 (s, 2H) 7.88 (s, 1H) 7.44 (s, 1H) 5.93 (s, 1H) 4.92-5.29 (m, 1H) 2.20 (s, 3H) 1.49 (d, 3H); m/z 350.

Workup

additionwas charged into a microwave reaction vessel
customThe vessel was sealed
customThe solvent was removed under reduced pressure
customthe residue was purified by Gilson (10-50% MeCN/H2O, 15 min)

Sources & evidence

ORD record: ord-6cda6834df30466eb196acb71a26e763
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088784B2

Reaction notes

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