2-Dimethylaminopyridine → 2-Chloro-N-(1-hydroxy-cycloheptylmethyl)-5-[5-methyl-1-(2-oxo-2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-3-yl]-benzamide

HRID 456881Notes

Reaction equation

HRID 456881 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([CH3:13])[N:10]([CH2:14][C:15]([OH:17])=O)[N:9]=2)=[CH:4][C:3]=1[C:18](=[O:29])[NH:19][CH2:20][C:21]1([OH:28])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.ON1C2C=[CH:37][CH:38]=[CH:39][C:34]=2[N:33]=N1.N1CCCC1.CN(C1C=CC=CN=1)C.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O>CN(C)C=O.C(N1C=CN=C1)(N1C=CN=C1)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([CH3:13])[N:10]([CH2:14][C:15](=[O:17])[N:33]3[CH2:34][CH2:39][CH2:38][CH2:37]3)[N:9]=2)=[CH:4][C:3]=1[C:18]([NH:19][CH2:20][C:21]1([OH:28])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)=[O:29]

Participants

8

Reactant 5

HCID 218852-DimethylaminopyridineHCID 31268PyrrolidineHCID 757711-HydroxybenzotriazoleHCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)HCID 58818193(3-{4-Chloro-3-[(1-hydroxy-cycloheptylmethyl)-carbamoyl]-phenyl}-5-methyl-pyrazol-1-yl)-acetic acid

Product 1

HCID 588181712-Chloro-N-(1-hydroxy-cycloheptylmethyl)-5-[5-methyl-1-(2-oxo-2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-3-yl]-benzamideYield 46.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 682631,1'-CarbonyldiimidazoleSolvent

Procedure

To a solution of (3-{4-chloro-3-[(1-hydroxy-cycloheptylmethyl)-carbamoyl]-phenyl}-5-methyl-pyrazol-1-yl)-acetic acid (41.9 mg, 0.1 mmol) in N,N-dimethylformamide (1 mL) was added a solution of 1-hydroxybenzotriazole (20.25 mg, 0.15 mmol) in N,N-dimethylformamide (0.5 mL) and carbonyldiimidazole on polystyrene (294 mg, 0.3 mmol). The mixture was shaken at room temperature for 10 minutes. Pyrrolidine (10.65 mg, 0.15 mmol) was added as a solution in N,N-dimethylformamide (1.5 mL). Polystyrene supported dimethylaminopyridine (152 mg, 0.22 mmol) was added and the mixture was shaken at room temperature for 16 h. MP-carbonate resin (139 mg, 0.4 mmol) was added and the mixture was shaken at room temperature for 3 h. The mixture was filtered, washed with methanol and concentrated in vacuo. The residue was purified by reverse phase chromatography to afford the title compound (22 mg). LCMS (m/z) 473.4 M+1.

Workup

  1. additionwas added
  2. stirringthe mixture was shaken at room temperature for 16 h
  3. stirringthe mixture was shaken at room temperature for 3 h
  4. filtrationThe mixture was filtered
  5. washwashed with methanol
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-295a16f3439c4fe3be08187e29f8a386
Source dataset
uspto-grants-2007_03
Patent number
US07186742B2

Reaction notes

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