Ammonia → 3-((R/S)-4-(6-Amino-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one

HRID 525389Notes

Reaction equation

HRID 525389 reaction equation
N.F[C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH2:14][CH2:13][C@H:12]([N:15]3[CH:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:18]([CH3:27])([CH3:26])[O:17][C:16]3=[O:28])[CH2:11][CH:10]=2)=[CH:5][C:4]=1[C:29]1[N:34]=[CH:33][CH:32]=[CH:31][N:30]=1.FC1[N:41]=CC(C2CC[C@@H](N3C(C4C=CC=CC=4)C(C)(C)OC3=O)CC=2)=CC=1C1N=CC=CN=1>CC(O)C.CS(C)=O>[NH2:41][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH2:14][CH2:13][CH:12]([N:15]3[CH:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:18]([CH3:27])([CH3:26])[O:17][C:16]3=[O:28])[CH2:11][CH:10]=2)=[CH:5][C:4]=1[C:29]1[N:34]=[CH:33][CH:32]=[CH:31][N:30]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 898137833-((R)-4-(6-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-oneHCID 898140903-((S)-4-(6-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one

Product 1

HCID 898139773-((R/S)-4-(6-Amino-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
130 °C

Procedure

A 2-mL glass microwave reaction vessel was charged with ammonia, (2 M solution in 2-propanol) (1.806 mL, 83 mmol, commercially available from Sigma-Aldrich, Milwaukee, Wis.) and a mixture of 3-((S)-4-(6-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one and 3-((R)-4-(6-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one (370 mg, 0.832 mmol) in DMSO (8.324 mL). The reaction mixture was stirred and heated at 130° C. for 3 days. LC-MS indicated clean and good conversion to the desired product with a small amount of starting material present. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc (3×). The combined organic layers were washed with water and brine and dried over MgSO4. The solution was filtered and concentrated under reduced pressure. The material thus obtained was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 100% EtOAc in heptane, to provide Example 131 (3-(4-(6-amino-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one) (210 mg, 0.476 mmol, 57.1% yield) as yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 8.87-8.92 (m, 4H), 8.60-8.64 (m, 2H), 8.20 (d, J=2.56 Hz, 1H), 8.17 (d, J=2.46 Hz, 1H), 7.34-7.46 (m, 9H), 7.25-7.34 (m, 4H), 5.95-5.98 (m, 1H), 5.83-5.89 (m, 1H), 4.70 (s, 1H), 4.67 (s, 1H), 3.59-3.77 (m, 2H), 2.60-2.75 (m, 1H), 1.90-2.43 (m, 8H), 1.71-1.80 (m, 1H), 1.47-1.53 (m, 8H), 0.78-0.87 (m, 6H). m/z (ESI) 442.2 (M+H)+.

Sources & evidence

ORD record
ord-d569391c764444eb85af2155c5a0380e
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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