Diisopropylethylamine → 4-Phenyl-pyrazole-1-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093777Notes

Reaction equation

HRID 1093777 reaction equation
Cl.[C:2]1([C:8]2[CH:9]=[N:10][NH:11][CH:12]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.Cl[C:23](Cl)([O:25]C(=O)OC(Cl)(Cl)Cl)Cl.Cl.[NH2:35][CH2:36][C:37]([N:39]1[CH2:44][CH2:43][CH:42]([O:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=2[Cl:52])[CH2:41][CH2:40]1)=[O:38]>C(Cl)Cl.O>[Cl:52][C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=1[O:45][CH:42]1[CH2:43][CH2:44][N:39]([C:37](=[O:38])[CH2:36][NH:35][C:23]([N:10]2[CH:9]=[C:8]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:12]=[N:11]2)=[O:25])[CH2:40][CH2:41]1

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 665915282-Amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochlorideHCID 665923304-phenyl-1H-pyrazole hydrochloride

Product 1

HCID 578744364-Phenyl-pyrazole-1-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 17.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

A mixture of 4-phenyl-1H-pyrazole hydrochloride (70 mg, 0.387 mmol), DIPEA (100 mg, 0.81 mmol) and DCM (5 mL) was added to a stirred solution of triphosgene (36 mg, 0.12 mmol) in DCM (2 mL) at room temperature. After 30 minutes, to the above solution, a mixture of 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared by method used for the synthesis of Intermediate 15) 118 mg, 0.3875 mmol), DIPEA (100 mg, 0.81 mmol) and DCM (5 mL) was added and the resulting mixture was stirred at room temperature for 1 hr. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure The residue was purified by preparative HPLC to afford 60 mg (17.6% Yield) of 4-phenyl-pyrazole-1-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]++: 439.15, 93.19%. 1H NMR (300 MHz, DMSO-d6): δ 8.8 (s, 1H), 8.4 (t, 1H), 8.35-8.3 (s, 1H), 7.8-7.72 (d, 2H), 7.48-7.38 (m, 3H), 7.35-7.24 (m, 3H), 7.0 (t, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.8-3.6 (m, 2H), 3.6-3.4 (m, 2H), 2.1-1.8 (m, 2H), 1.8-1.6 (m, 2H).

Workup

  1. customprepared by method
  2. additionwas added
  3. extractionthe product was extracted with EtOAc
  4. washthe organic layer was washed with brine
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure The residue
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-1aa6dde2f1404574ae75ed7a98c19c07
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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