(S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one → (S)-3-(2-((S)-1-(4-hydroxyphenyl)ethylamino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one

HRID 1850187Notes

Reaction equation

HRID 1850187 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]2=[O:16])[CH:5]=[CH:4][N:3]=1.Cl.[NH2:18][C@H:19]([C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1)[CH3:20]>CS(C)=O.CCOC(C)=O>[OH:27][C:24]1[CH:25]=[CH:26][C:21]([C@@H:19]([NH:18][C:2]2[N:7]=[C:6]([N:8]3[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]3=[O:16])[CH:5]=[CH:4][N:3]=2)[CH3:20])=[CH:22][CH:23]=1

Participants

5

Reactant 2

HCID 86730167(S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-oneHCID 86730215(S)-4-(1-aminoethyl)phenol hydrochloride

Product 1

HCID 86730214(S)-3-(2-((S)-1-(4-hydroxyphenyl)ethylamino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-oneYield 5.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one (42 mg, 0.17 mmol), (S)-4-(1-aminoethyl)phenol hydrochloride (107 mg, 0.616 mmol, 3.5 equiv) and iPr2Net (0.121 mL, 0.695 mmol, 4.0 equiv) in DMSO (1 mL) was heated at 110° C. for 3 h and at 130° C. for additional 2 h. The reaction mixture was diluted with EtOAc (8 mL) and washed with water (30 mL). After separation, the aqueous phase was extracted with EtOAc (3×8 mL). Combined organics were dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane 10 to 80%) provided (S)-3-(2-((S)-1-(4-hydroxyphenyl)ethylamino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one (3 mg) in 5% yield. 1H NMR (400 MHz, CD3OD) δ 8.11 (d, J=5.8 Hz, 1H), 7.33 (d, J=5.8 Hz, 1H), 7.12 (d, J 8.1 Hz, 2H), 6.72-6.68 (m, 2H), 4.95 (q, J=6.9 Hz, 1H), 4.69-4.65 (m, 1H), 4.35-4.28 (m, 2H), 1.47 (d, J=7.1 Hz, 3H), 0.75 (br s, 3H), 0.62 (br s, 3H); HRMS(B) m/z 343.1776 (M+H)+.

Workup

  1. washwashed with water (30 mL)
  2. customAfter separation
  3. extractionthe aqueous phase was extracted with EtOAc (3×8 mL)
  4. dry with materialCombined organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-64eff8d512b84d068f51ec9b5ead2439
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

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