Potassium Carbonate → HCID 57513762, compound

HRID 2368423Notes

Reaction equation

HRID 2368423 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]([CH3:37])([CH3:36])[C:15]([NH:17][C:18]1[S:19][C:20]([C:27](=[O:35])[C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=1)=[O:16].C([O-])([O-])=O.[K+].[K+].[CH2:44]1[CH2:50][O:49][CH2:48][CH2:47][NH:46][CH2:45]1.Cl>O.ClCCl.N1C=CC=CC=1>[F:34][C:31]1[CH:32]=[CH:33][C:28]([C:27]([C:20]2[S:19][C:18]([NH:17][C:15]([C:14]([NH:13][C:2]([N:46]3[CH2:45][CH2:44][CH2:50][O:49][CH2:48][CH2:47]3)=[O:4])([CH3:37])[CH3:36])=[O:16])=[N:22][C:21]=2[C:23]([F:25])([F:26])[F:24])=[O:35])=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 94429TriphosgeneHCID 230902141,4-Oxazepane hydrochlorideHCID 57513835HCID 57513835, compound

Product 1

HCID 57513762HCID 57513762, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of triphosgene (79 mg, 0.27 mmol) and 2-Amino-N-[5-(4-fluoro-benzoyl)-4-trifluoromethyl-thiazol-2-yl]-2-methyl-propionamide (100 mg, 0.266 mmol), K2CO3 (147 mg, 1.07 mmol) in water (3 mL) and dichloromethane (3 mL) was stirred at RT for 1 h, and water layer was separated, and dichloromethane layer was dried over Na2SO4 and concentrated to give the crude intermediate, which was taken up in pyridine (10 mL). Homomorpholine HCl salt (269 mg, 2.66 mmol) was basified by partitioning between ethyl acetate and aqueous KOH, and after evaporation of the solvent, it was added to the intermediate above. The mixture was heated at 80° C. for 18 h, and most of pyridine was removed under vacuum, and the mixture was partitioned between ethyl acetate and 1 M HCl. The combined organic extract was dried over Na2SO4, concentrated and chromatographed to give the title compound. m/z 503.0 (MH+), 1H NMR (CDCl3) δ 11.4 (s, 1H), 7.92 (dd, J=8, 4 Hz, 2H), 7.16 (t, J=8 Hz, 2H), 4.64 (s, 1H), 3.80-3.75 (m, 4H), 3.60-3.50 (m, 4H), 2.02-1.93 (m, 2H), 1.63 (s, 6H). Retention time 1.31 min (method A).

Workup

  1. customwater layer was separated
  2. dry with materialdichloromethane layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customto give the crude intermediate, which
  5. customby partitioning between ethyl acetate and aqueous KOH
  6. customafter evaporation of the solvent, it
  7. additionwas added to the intermediate above
  8. temperatureThe mixture was heated at 80° C. for 18 h
  9. custommost of pyridine was removed under vacuum
  10. customthe mixture was partitioned between ethyl acetate and 1 M HCl
  11. extractionThe combined organic extract
  12. dry with materialwas dried over Na2SO4
  13. concentrationconcentrated
  14. customchromatographed

Sources & evidence

ORD record
ord-1b6cd085ae094ea3a0295c6a04385066
Source dataset
uspto-grants-2014_04
Patent number
US08703761B2

Reaction notes

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