Diisopropylethylamine → (4R)-3-[2-[[1-[3-(4-Chlorophenyl)-5-isoxazolyl]ethyl]amino]-4-pyrimidinyl]-4-[(1R)-1-(1,1-dimethylethoxy)ethyl]-2-oxazolidinone

HRID 57484Notes

Reaction equation

HRID 57484 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([CH:13]([NH2:15])[CH3:14])[O:10][N:9]=2)=[CH:4][CH:3]=1.[C:16]([O: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])([CH3:19])([CH3:18])[CH3:17].C(N(C(C)C)C(C)C)C>CS(C)=O.CCOC(C)=O>[C:16]([O: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:15][CH:13]([C:11]2[O:10][N:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH:12]=2)[CH3:14])[N:30]=1)[CH3:22])([CH3:17])([CH3:18])[CH3:19]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 838498741-(3-(4-Chlorophenyl)isoxazol-5-yl)ethanamineHCID 90415866(R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one

Product 1

HCID 90415932(4R)-3-[2-[[1-[3-(4-Chlorophenyl)-5-isoxazolyl]ethyl]amino]-4-pyrimidinyl]-4-[(1R)-1-(1,1-dimethylethoxy)ethyl]-2-oxazolidinoneYield 37.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 1-(3-(4-chlorophenyl)isoxazol-5-yl)ethanamine (610 mg, 2.74 mmol) and (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one (774 mg, 2.74 mmol) in DMSO (5 ml) was added N-ethyl-N-isopropylpropan-2-amine (2 eq, 0.96 mL, 5.48 mmol) and heated in a microwave at 120° C. for 2 hours. Dilute with EtOAc (50 ml), wash with water (50 ml), brine (50 ml), concentrate in vacuo. Flash column chromatography (silica, 40 g) eluting w/0-25% EtOAc/DCM afforded 500 mg of white solid: 1H NMR (400 MHz, CDCl3) b 8.24 (dd, J=5.8, 1.6 Hz, 1H), 7.80-7.65 (m, 2H), 7.58 (dd, J=5.8, 1.6 Hz, 1H), 7.49-7.37 (m, 2H), 6.48-6.35 (m, 1H), 5.66-5.44 (m, 1H), 4.71 (dddd, J=9.8, 8.5, 4.6, 3.0 Hz, 1H), 4.63 (ddd, J=9.4, 3.1, 2.1 Hz, 1H), 4.50-4.26 (m, 2H), 1.71 (s, 1H), 1.25 (s, 5H), 1.15 (s, 5H), 1.03 (dd, J=22.4, 6.4 Hz, 3H), 5.44-5.13 (m, 1H). HRMS(B) tR=3.36 min; m/z 485.1830

Workup

  1. washwash with water (50 ml), brine (50 ml)
  2. concentrationconcentrate in vacuo
  3. washFlash column chromatography (silica, 40 g) eluting w/0-25% EtOAc/DCM

Sources & evidence

ORD record
ord-7d29d564ae4b4bd8a27be73cb98d1ed2
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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