Triethylamine → HCID 57485438, compound

HRID 1020345Notes

Reaction equation

[Br:1][C:2]1[O:3][C:4]([C:11](Cl)=[O:12])=[C:5]([C:7]([F:10])([F:9])[F:8])[N:6]=1.[NH2:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]2[CH2:26][CH2:25][CH:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:23][CH2:22]2)=[N:19][CH:20]=1.C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[O:3][C:4]([C:11]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([N:21]3[CH2:22][CH2:23][CH:24]([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH2:25][CH2:26]3)=[N:19][CH:20]=2)=[O:12])=[C:5]([C:7]([F:10])([F:9])[F:8])[N:6]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 2-bromo-4-trifluoromethyloxazole-5-carbonyl chloride (A-39) (0.34 g, 1.2 mmol) and 1-(5-aminopyridin-2-yl)-4-phenylpiperidine (B-6) (0.25 g, 1.0 mmol) in CH2Cl2 (10 mL) was cooled to −78° C. then triethyl amine (0.16 mL, 1.2 mmol) was added. The reaction mixture was stirred for 2 h while the temperature was warmed slowly up to 0° C. The solvent was concentrated, and the residue was purified by chromatography on a silica-gel column (eluant: 0-50% EtOAc/hexane gradient) to yield 1-(5-(2-bromo-4-(trifluoromethyl)oxazole-5-carboxamido)pyridin-2-yl)-4-phenylpiperidine (A-40) (0.19 g, 35% yield) as a yellow solid. Note: the product A-40 contains compound with the bromine atom exchanged for a chlorine atom. 1H NMR (500 MHz, CDCl3) δ 9.58 (br s, 1H), 8.59 (br s, 1H), 8.34 (dd, 1H, J=9.5, 1.8 Hz), 7.35 (m, 2H), 7.30-7.22 (m, 3H), 6.89 (d, 1H, J=9.4 Hz), 4.42 (d, 2H, J=13.3 Hz), 3.17 (t, 2H, J=12.7 Hz), 2.85 (m, 1H), 2.05 (m, 2H), 1.84 (m, 2H); LCMS (ESI) calcd for [M+1]+ for chloride 451.1. found 451.4.

Workup

concentrationThe solvent was concentrated
customthe residue was purified by chromatography on a silica-gel column (eluant: 0-50% EtOAc/hexane gradient)

Sources & evidence

ORD record: ord-3ead19f0a7fa49f4b7607ff8efa775c4
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716312B2

Reaction notes

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