Diisopropylethylamine → (4R)-4-[(1S)-1-fluoroethyl]-3-[2-[[(1S)-1-[4-methyl-5-[2-(trifluoromethyl)pyridin-4-yl]pyridin-2-yl]ethyl]amino]pyrimidin-4-yl]-1,3-oxazolidin-2-one

HRID 57508Notes

Reaction equation

HRID 57508 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C@@H:8]([NH2:10])[CH3:9])[N:5]=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][N:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=1.[F:21][C@H:22]([C@H:24]1[CH2:28][O:27][C:26](=[O:29])[N:25]1[C:30]1[CH:35]=[CH:34][N:33]=[C:32](F)[N:31]=1)[CH3:23].CCN(C(C)C)C(C)C>CS(C)=O>[F:21][C@H:22]([C@H:24]1[CH2:28][O:27][C:26](=[O:29])[N:25]1[C:30]1[CH:35]=[CH:34][N:33]=[C:32]([NH:10][C@H:8]([C:6]2[N:5]=[CH:4][C:3]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([C:17]([F:19])([F:20])[F:18])[CH:12]=3)=[C:2]([CH3:1])[CH:7]=2)[CH3:9])[N:31]=1)[CH3:23]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 90415299(R)-4-((S)-1-Fluoroethyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-oneHCID 90423562(S)-1-(4-Methyl-2'-(trifluoromethyl)-[3,4'-bipyridin]-6-yl)ethan-1-amine

Product 1

HCID 90415637(4R)-4-[(1S)-1-fluoroethyl]-3-[2-[[(1S)-1-[4-methyl-5-[2-(trifluoromethyl)pyridin-4-yl]pyridin-2-yl]ethyl]amino]pyrimidin-4-yl]-1,3-oxazolidin-2-oneYield 28.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of (S)-1-(4-methyl-2′-(trifluoromethyl)-[3,4′-bipyridin]-6-yl)ethanamine (28.1 mg, 0.1 mmol), (R)-4-((S)-1-fluoroethyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one (22.9 mg, 0.100 mmol) and DIPEA (52.4 μl, 0.300 mmol) in DMSO (Volume: 500 μl) was heated at 110° C. for 1 hr. The solution was then cooled to rt, and RP-HPLC (acetonitrile:water) purification provided a white solid. This material was purified again with flash column chromatography (0-10% MeOH/EtOAc) to give 14 mg (R)-4-((S)-1-fluoroethyl)-3-(2-(((S)-1-(4-methyl-2′-(trifluoromethyl)-[3,4′-bipyridin]-6-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one as a white solid. 1H NMR (400 MHz, MeOD) δ 8.81 (d, J=5.0 Hz, 1H), 8.41 (s, 1H), 8.18 (s, 1H), 7.86 (s, 1H), 7.69 (dd, J=5.0, 1.6 Hz, 1H), 7.44 (s, 1H), 7.41 (d, J=5.8 Hz, 1H), 5.08 (br s, 1H), 4.73 (br d, J=26.0 Hz, 1H), 4.56-4.27 (m, 3H), 2.32 (s, 3H), 1.58 (d, J=7.1 Hz, 3H), 1.12 (br s, 3H); HRMS (B) m/z 491.1782 (M+H)+. Anal. RP-HPLC tR=3.42 min. Purity 100%/100%.

Workup

  1. customRP-HPLC (acetonitrile:water) purification
  2. customprovided a white solid
  3. customThis material was purified again with flash column chromatography (0-10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-f5d784fb87b74c13955fc94c8a4b6030
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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