Cyclohexylamine → HCID 59516070, compound

HRID 1799402Notes

Reaction equation

HRID 1799402 reaction equation
[CH3:1][O:2][C:3]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]([S:17][CH2:18][CH2:19][CH3:20])=[C:15]([C:21]([OH:23])=O)[CH:14]=[N:13]2)=[CH:8][CH:7]=1)=[O:4].C(Cl)(=O)C(Cl)=O.[CH:30]1([NH2:36])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[CH:30]1([NH:36][C:21]([C:15]2[CH:14]=[N:13][N:12]([C:9]3[CH:8]=[CH:7][C:6]([CH2:5][C:3]([O:2][CH3:1])=[O:4])=[CH:11][CH:10]=3)[C:16]=2[S:17][CH2:18][CH2:19][CH3:20])=[O:23])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

8

Reactant 4

HCID 7965CyclohexylamineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 59516146HCID 59516146, compound2×

Product 1

HCID 59516070HCID 59516070, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1-[4-(methoxycarbonylmethyl)phenyl]-5-propylsulfanyl-pyrazole-4-carboxylic acid (Intermediate #35) (220 mg, 0.66 mmol) was dissolved in DCM (5 mL) and 1 drop of DMF added. Oxalyl chloride (176 μL, 1.96 mmol) was added and the mixture stirred at ambient temperature for 3 h. Volatiles were removed by evaporation under reduced pressure and the resulting gum re-dissolved in DCM (2 mL) and added at ambient temperature to a solution of cyclohexylamine (66 mg, 0.66 mmol) and DIPEA (230 μL, 1.32 mmol) in DCM (5 mL). The reaction mixture was stirred at ambient temperature for 2 h, diluted with EtOAc (50 mL) and washed with water (2×10 mL) and brine (10 mL), dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash chromatography on to silica gel (elution gradient 0-100% EtOAc in isohexane) to afford methyl 2-[4-[4-(cyclohexylcarbamoyl)-5-propylsulfanyl-pyrazol-1-yl]phenyl]acetate as a white solid. (220 mg, 88%)

Workup

  1. customVolatiles were removed by evaporation under reduced pressure
  2. dissolutionthe resulting gum re-dissolved in DCM (2 mL)
  3. stirringThe reaction mixture was stirred at ambient temperature for 2 h
  4. washwashed with water (2×10 mL) and brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated under reduced pressure
  7. customThe residue was purified by flash chromatography on to silica gel (elution gradient 0-100% EtOAc in isohexane)

Sources & evidence

ORD record
ord-a59be966d06846f9bec833e80695a006
Source dataset
uspto-grants-2013_01
Patent number
US08344016B2

Reaction notes

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