Diisopropylethylamine → [5-tert-Butyl-2-(3-morpholin-4-yl-phenyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

HRID 75609Notes

Reaction equation

HRID 75609 reaction equation
[Cl:1][C:2]([Cl:9])([Cl:8])[CH2:3][O:4][C:5](Cl)=[O:6].[C:10]([C:14]1[CH:15]=[C:16]([NH2:31])[N:17]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:20]=2)[N:18]=1)([CH3:13])([CH3:12])[CH3:11].CCN(C(C)C)C(C)C>C1COCC1.O>[Cl:1][C:2]([Cl:9])([Cl:8])[CH2:3][O:4][C:5](=[O:6])[NH:31][C:16]1[N:17]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:20]=2)[N:18]=[C:14]([C:10]([CH3:11])([CH3:12])[CH3:13])[CH:15]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 870632,2,2-Trichloroethyl chloroformateHCID 86686708HCID 86686708, compound

Product 1

HCID 86686709[5-tert-Butyl-2-(3-morpholin-4-yl-phenyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl esterYield 46.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2,2,2-Trichloroethylchloroformate (175 mg, 0.82 mmol) was added dropwise to a solution of Intermediate 23d (190 mg, 0.63 mmol) and DIPEA (244 mg, 1.89 mmol) in THF (10 mL), and the mixture stirred at RT for 1.5 h. The mixture was diluted with water and extracted with EtOAc (×2). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-50% EtOAc in cyclohexane, to give the title compound (140 mg, 46%). LCMS (Method 4): Rt 3.94, m/z 475 [MH+].

Workup

  1. extractionextracted with EtOAc (×2)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-7447b043c21849b1bac8cc0797da5bd1
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

Loading…