Diisopropylethylamine → (R)-4-((S)-1-fluoroethyl)-3-(2-(((S)-1-(2'-(trifluoromethyl)-[3,4'-bipyridin]-6-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one

HRID 57510Notes

Reaction equation

HRID 57510 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[C:7]([C:9]2[CH:10]=[N:11][C:12]([C@@H:15]([NH2:17])[CH3:16])=[CH:13][CH:14]=2)[CH:6]=[CH:5][N:4]=1.[F:20][C@H:21]([C@H:23]1[CH2:27][O:26][C:25](=[O:28])[N:24]1[C:29]1[CH:34]=[CH:33][N:32]=[C:31](F)[N:30]=1)[CH3:22].CCN(C(C)C)C(C)C>CS(C)=O>[F:20][C@H:21]([C@H:23]1[CH2:27][O:26][C:25](=[O:28])[N:24]1[C:29]1[CH:34]=[CH:33][N:32]=[C:31]([NH:17][C@H:15]([C:12]2[N:11]=[CH:10][C:9]([C:7]3[CH:6]=[CH:5][N:4]=[C:3]([C:2]([F:1])([F:18])[F:19])[CH:8]=3)=[CH:14][CH:13]=2)[CH3:16])[N:30]=1)[CH3:22]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 90413968(S)-1-(2'-(trifluoromethyl)-[3,4'-bipyridin]-6-yl)ethanamineHCID 90415299(R)-4-((S)-1-Fluoroethyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one

Product 1

HCID 90416189(R)-4-((S)-1-fluoroethyl)-3-(2-(((S)-1-(2'-(trifluoromethyl)-[3,4'-bipyridin]-6-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-oneYield 67.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of (S)-1-(2′-(trifluoromethyl)-[3,4′-bipyridin]-6-yl)ethanamine (27 mg, 0.10 mmol), (R)-4-((S)-1-fluoroethyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one (23 mg, 0.10 mmol) and DIPEA (52.4 μl, 0.30 mmol) in DMSO (500 μl) was heated at 110° C. for 1 hr. The solution was then cooled to rt and RP-HPLC purification (acetonitrile:water) provided the 32 mg of the major product as a white solid. 1H NMR (400 MHz, MeOD) δ 8.98 (s, 1H), 8.79 (d, J=5.1 Hz, 1H), 8.23 (dd, J=8.2, 2.4 Hz, 1H), 8.17 (br s, 1H), 8.17-8.12 (m, 1H), 7.98 (dd, J=5.1, 1.7 Hz, 1H), 7.59 (d, J=8.3 Hz, 1H), 7.40 (d, J=5.8 Hz, 1H), 5.11 (br s, 1H), 4.69 (br d, J=27.2 Hz, 1H), 4.55-4.12 (m, 3H), 1.60 (d, J=7.1 Hz, 3H), 1.03 (br s, 3H); HRMS (B) m/z 477.1699 (M+H)+.

Workup

  1. customRP-HPLC purification (acetonitrile:water)

Sources & evidence

ORD record
ord-fc14530196d343a19993d1a3ae2a5cbf
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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