Sodium Bicarbonate → 1-[4-[4-[(5R)-4,5-dihydro-5-phenyl-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-N-[2,5-dimethylphenyl]carboxamide

HRID 2096031Notes

Reaction equation

HRID 2096031 reaction equation
CC1C=CC(C)=CC=1[NH:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([C:18](=[S:20])[NH2:19])[CH2:14][CH2:13]1)=O.Br[CH2:22][C:23]([C:25]1[CH2:29][C@H:28]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[O:27][N:26]=1)=O.[C:36](=[O:39])(O)[O-].[Na+]>CC(C)=O>[C:30]1([C@@H:28]2[O:27][N:26]=[C:25]([C:23]3[N:19]=[C:18]([CH:15]4[CH2:14][CH2:13][N:12]([C:10]5([NH:9][CH:36]=[O:39])[CH:31]=[C:30]([CH3:35])[CH:28]=[CH:29][CH:25]5[CH3:23])[CH2:17][CH2:16]4)[S:20][CH:22]=3)[CH2:29]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 866312472-bromo-1-[(5R)-4,5-dihydro-5-phenyl-3-isoxazolyl]ethanoneHCID 86645615N-(2,5-dimethylphenyl)-4-thiocarbamoylpiperidine-carboxamide2×

Product 1

HCID 1317305961-[4-[4-[(5R)-4,5-dihydro-5-phenyl-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-N-[2,5-dimethylphenyl]carboxamide

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
45 °C

Procedure

A mixture of N-(2,5-dimethylphenyl)-4-thiocarbamoylpiperidine carboxamide (i.e. the product of Example 14, Step B) (291 mg, 1.0 mmol) and 409 (i.e. the product of Example 12, Step E) (268 mg, 1.0 mmol) in acetone (10 mL) was vortexed for 16 h and then heated at 45° C. for 1 h. The reaction mixture was allowed to cool to room temperature, treated with solid sodium bicarbonate (168 mg, 2.0 mmol), and stirred for 1 h. The reaction mixture was then concentrated under reduced pressure, diluted with ethyl acetate, washed with water and brine, dried (MgSO4), and concentrated under reduced pressure to give the title product as a pale-yellow foam. The sample was dissolved in methyl acetate (2 mL) and allowed to sit at room temperature and then at 0° C. to give 220 mg of colorless crystals melting at 120-125° C. A second preparation was crystallized from methanol to give large prisms melting at 121-124° C.

Workup

  1. temperatureto cool to room temperature
  2. concentrationThe reaction mixture was then concentrated under reduced pressure
  3. additiondiluted with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0679f54b3ef04b44b9ff53f8b0578d78
Source dataset
uspto-grants-2013_05
Patent number
US08449898B2

Reaction notes

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