Pyridine → 1,1-dimethylethyl 5-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-carboxylate

HRID 75184Notes

Reaction equation

HRID 75184 reaction equation
[NH2:1][C:2](=[S:18])[N:3]1[CH2:7][CH:6]2[CH2:8][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][CH:5]2[CH2:4]1.Cl[CH2:20][C:21]([C:23]1[CH2:27][CH:26]([C:28]2[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:29]=2[F:35])[O:25][N:24]=1)=O.N1C=CC=CC=1>C(Cl)(Cl)Cl>[F:35][C:29]1[CH:30]=[CH:31][CH:32]=[C:33]([F:34])[C:28]=1[CH:26]1[O:25][N:24]=[C:23]([C:21]2[N:1]=[C:2]([N:3]3[CH2:7][CH:6]4[CH2:8][N:9]([C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12])[CH2:10][CH:5]4[CH2:4]3)[S:18][CH:20]=2)[CH2:27]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 866744762-Chloro-1-(5-(2,6-difluorophenyl)-4,5-dihydroisoxazol-3-yl)ethan-1-one2×HCID 86674477HCID 86674477, compound2×

Product 1

HCID 673413561,1-dimethylethyl 5-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-carboxylate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 1,1-dimethylethyl 5-(aminothioxomethyl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (i.e. the product of Step A) (0.5 g, 18.42 mmol) in chloroform (20 mL) was added 2-chloro-1-[5-(2,6difluorophenyl)-4,5-dihydroisoxazol-3-yl]ethanone (i.e. the product of Step B) (0.478 g, 18.42 mmol) and pyridine (0.29 g, 37.12 mmol) at room temperature. The reaction mixture was heated at 90° C. for 5 h, cooled to room temperature and concentrated under reduced pressure. The resulting material was dissolved in ethyl acetate (100 mL) and washed with water (100 mL) and saturated aqueous sodium chloride solution (100 mL) and concentrated under reduced pressure. The resulting material was purified by column chromatography (1% methanol/chloroform as eluant) to provide the title product as white solid (0.7 g) melting at 78.9-80.2° C.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe resulting material was dissolved in ethyl acetate (100 mL)
  4. washwashed with water (100 mL) and saturated aqueous sodium chloride solution (100 mL)
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting material was purified by column chromatography (1% methanol/chloroform as eluant)

Sources & evidence

ORD record
ord-c50cd64e2ba84c46a2ad19021257f757
Source dataset
uspto-grants-2014_09
Patent number
US08835427B2

Reaction notes

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