Triphenylphosphine → N-{3-[2-(bromomethyl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine

HRID 410624Notes

Reaction equation

[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([CH2:24]O)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C(=O)N([Br:52])C(=O)C1>ClCCl>[Br:52][CH2:24][C:22]1[S:23][C:19]([C:4]2[CH:5]=[C:6]([NH:8][C:9]3[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=3)[CH:7]=[C:2]([CH3:1])[CH:3]=2)=[CH:20][N:21]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To [5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methanol (0.13 g, 0.34 mmol) was added dichloromethane (3.5 mL) and triphenylphosphine (0.11 g, 0.41 mmol). The solution was cooled to 0° C. and n-bromosuccinimide (0.067 g, 0.38 mmol) was added and the reaction was allowed to warm slowly to room temperature. Once the reaction was complete, silica gel (1.3 g) was added and the slurry was concentrated. The solid was purified by silica gel chromatography to yield N-{3-[2-(bromomethyl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (0.072 g, 49%). MS ESI: [M+H]+ m/z 430.9. 1H NMR (500 MHz, DMSO-d6) δ 10.29 (s, 1H), 8.84 (d, J=4.9, 1H), 8.07 (s, 1H), 7.99 (s, 1H), 7.49 (s, 1H), 7.29 (d, J=4.9, 1H), 7.21 (s, 1H), 5.04 (s, 2H), 2.32 (s, 3H). rhSYK activity=+++

Workup

temperatureto warm slowly to room temperature
additionsilica gel (1.3 g) was added
concentrationthe slurry was concentrated
customThe solid was purified by silica gel chromatography

Sources & evidence

ORD record: ord-2d2012c7b7fb4b62bdb32cdff97a8e62
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759366B2

Reaction notes

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