p-Toluenesulfonic acid → 1-[((1S,2S)-2-benzyloxy-cyclohexylcarbamoyl)-methyl]-5-(3-fluoro-5-trifluoromethyl-benzyloxy)-1H-pyrazole-3-carboxylic acid ethyl ester

HRID 1242866Notes

Reaction equation

HRID 1242866 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([O:11][CH2:12][C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15]([F:23])[CH:14]=2)[N:8]([CH2:24][C:25](O)=[O:26])[N:7]=1)=[O:5])[CH3:2].[CH2:28]([O:35][C@H:36]1[CH2:41][CH2:40][CH2:39][CH2:38][C@@H:37]1[NH2:42])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.ON1C2C=CC=CC=2N=N1.N=C=N.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O.CC1C=CC(S(O)(=O)=O)=CC=1>O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([O:11][CH2:12][C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:20])[F:21])[CH:16]=[C:15]([F:23])[CH:14]=2)[N:8]([CH2:24][C:25](=[O:26])[NH:42][C@H:37]2[CH2:38][CH2:39][CH2:40][CH2:41][C@@H:36]2[O:35][CH2:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

8

Reactant 6

HCID 6101p-Toluenesulfonic acidHCID 757711-HydroxybenzotriazoleHCID 160435CarbodiimideHCID 11908838(1S,2S)-trans-2-Benzyloxy-cyclohexylamineHCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)HCID 693640081-carboxymethyl-5-(3-fluoro-5-trifluoromethyl-benzyloxy)-1H-pyrazole-3-carboxylic acid ethyl ester

Product 1

HCID 586467151-[((1S,2S)-2-benzyloxy-cyclohexylcarbamoyl)-methyl]-5-(3-fluoro-5-trifluoromethyl-benzyloxy)-1H-pyrazole-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 58.5 mg (0.15 mmol) of 1-carboxymethyl-5-(3-fluoro-5-trifluoromethyl-benzyloxy)-1H-pyrazole-3-carboxylic acid ethyl ester (3) in 5 mL of tetrahydrofuran was added 123 mg (0.60 mmol) of (1S, 2S)-2-benzyloxy-cyclohexylamine, 40 mg (0.30 mmol) of 1-hydroxybenzotriazole (HOBt) and 500 mg (0.60 mmol) of PS-carbodiimide resin, and the mixture was shaken at rt overnight. The reaction mixture was then treated with 200 mg (0.60 mmol) of MP-carbonate resin and 225 mg (0.9 mmol) of PS-TsOH resin, and shaken at rt for 4 h. The resulting mixture was filtered and washed with tetrahydrofuran (2×2 mL), and the combined tetrahydrofuran extracts were concentrated to afford crude 1-[((1S, 2S)-2-benzyloxy-cyclohexylcarbamoyl)-methyl]-5-(3-fluoro-5-trifluoromethyl-benzyloxy)-1H-pyrazole-3-carboxylic acid ethyl ester (4) which was used in the next reaction without any further purification.

Workup

  1. stirringshaken at rt for 4 h
  2. filtrationThe resulting mixture was filtered
  3. washwashed with tetrahydrofuran (2×2 mL)
  4. concentrationthe combined tetrahydrofuran extracts were concentrated

Sources & evidence

ORD record
ord-99ba6c68263e4d5f80203c8707430db6
Source dataset
uspto-grants-2006_10
Patent number
US07115749B2

Reaction notes

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