Hydrochloric Acid → HCID 71736385, compound

HRID 525335Notes

Reaction equation

HRID 525335 reaction equation
F[C:2]1[C:7]([C:8]2[CH2:13][CH2:12][C@@H:11]([N:14]3[C@@H:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:17]([CH3:26])([CH3:25])[O:16][C:15]3=[O:27])[CH2:10][CH:9]=2)=[CH:6][C:5]([C:28]2[N:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:4][N:3]=1.FC1C(C2CC[C@H](N3[C@@H](C4C=CC=CC=4)C(C)(C)[O:49]C3=O)CC=2)=CC(C2N=CC=CN=2)=CN=1.O1CCOCC1.Cl>O>[CH3:25][C:17]1([CH3:26])[O:16][C:15](=[O:27])[N:14]([C@H:11]2[CH2:12][CH2:13][C:8]([C:7]3[C:2](=[O:49])[NH:3][CH:4]=[C:5]([C:28]4[N:33]=[CH:32][CH:31]=[CH:30][N:29]=4)[CH:6]=3)=[CH:9][CH2:10]2)[C@H:18]1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 89813729HCID 89813729, compoundHCID 89813897HCID 89813897, compound

Product 1

HCID 71736385HCID 71736385, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A resealable tube was charged with a mixture of (S)-3-((R)-4-(2-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one and (S)-3-((S)-4-(2-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.090 g, 0.202 mmol), dioxane (3.0 mL), and water (1.0 mL). Concentrated HCl (37%) (0.25 mL) was added, the system was flushed with argon, the tube was sealed, and the reaction mixture was stirred at 100° C. for 2 hours. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3 solution. The aqueous phase was washed and extracted with EtOAc. The combined organic phases were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford an off-white solid. This material was purified via SFC separation (Chiralpak AD-H column (2×15 cm), eluting with 25% MeOH (0.2% DEA)/CO2, 100 bar, 70 mL/min, 220 nM. Injection volume 0.5 mL, 9 mg/mL MeOH) to afford (S)-5,5-dimethyl-3-((S)-4-(2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)cyclohex-3-en-1-yl)-4-phenyloxazolidin-2-one (0.026 g, 0.059 mmol, 29% yield) as a white solid (first eluting peak, structure arbitrarily assigned). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.82 (s, 3H), 1.50 (s, 3H), 1.86-2.23 (m, 4H), 2.27-2.48 (m, 1H), 2.54-2.70 (m, 1H), 3.56-3.84 (m, 1H), 4.51-4.89 (m, 1H), 6.35 (br. s., 1H), 7.14-7.62 (m, 6H), 8.05-8.36 (m, 2H), 8.67-8.90 (m, 2H), 11.96 (br. s., 1H). m/z (ESI) 443 (M+H)+.

Workup

  1. customthe system was flushed with argon
  2. customthe tube was sealed
  3. customThe reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3 solution
  4. washThe aqueous phase was washed
  5. extractionextracted with EtOAc
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford an off-white solid
  11. customThis material was purified via SFC separation (Chiralpak AD-H column (2×15 cm), eluting with 25% MeOH (0.2% DEA)/CO2, 100 bar, 70 mL/min, 220 nM. Injection volume 0.5 mL, 9 mg/mL MeOH)

Sources & evidence

ORD record
ord-60d10bc9884a4bb6ba91dfcb39759316
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

Loading…