Water → HCID 11575871, compound

HRID 2113699Notes

Reaction equation

HRID 2113699 reaction equation
[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:15]4[N:19]([C:20]5[CH:28]=[CH:27][C:23](C(O)=O)=[CH:22][CH:21]=5)[N:18]=[CH:17][CH:16]=4)[CH:13]=3)[C:8]([CH2:29][CH3:30])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:31]1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[CH3:44][NH:45][O:46][CH3:47].[OH2:48]>C(Cl)Cl.C(OCC)(=O)C>[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:15]4[N:19]([C:20]5[CH:21]=[CH:22][C:23]([C:44]([N:45]([O:46][CH3:47])[CH3:31])=[O:48])=[CH:27][CH:28]=5)[N:18]=[CH:17][CH:16]=4)[CH:13]=3)[C:8]([CH2:29][CH3:30])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 11524159HCID 11524159, compound

Product 1

HCID 11575871HCID 11575871, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-[5-(1-cyclopentyl-3-ethyl-1H-indazol-6-yl)-1H-pyrazol-1-yl]benzoic acid (100.0 mg, 0.250 mmol) in 1.2 mL of methylene chloride under at atmosphere of argon at 0° C. was added N,N-carbonyldiimidazole (48.2 mg, 0.297 mmol) with stirring. After 30 minutes N,O-dimethylhydroxylamine hydrochloride (59.9 mg, 0.614 mmol) was added and the resultant suspension was warmed to room temperature, stirred for 24 hours and then 10 mL of water and 10 mL of ethyl acetate were added. The organic layer was separated, washed with 10 mL of 1N NaOH, 10 mL of water, 10 mL of brine, dried over sodium sulfate, and filtered. Approximately 2 g of silica gel were added and the mixture was evaporated to dryness under reduced pressure. The residue was purified by column chromatography over silica gel eluting with a linear gradient from 10% ethyl acetate in hexanes to 50% ethyl acetate in hexanes over 20 minutes to yield 4-[5-(1-cyclopentyl-3-ethyl-1H-indazol-6-yl)-1H-pyrazol-1-yl]-N-methoxy-N-methylbenzamide (55 mg, 50%) as a white solid.

Workup

  1. stirringstirred for 24 hours
  2. customThe organic layer was separated
  3. washwashed with 10 mL of 1N NaOH, 10 mL of water, 10 mL of brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. additionApproximately 2 g of silica gel were added
  7. customthe mixture was evaporated to dryness under reduced pressure
  8. customThe residue was purified by column chromatography over silica gel eluting with a linear gradient from 10% ethyl acetate in hexanes to 50% ethyl acetate in hexanes over 20 minutes

Sources & evidence

ORD record
ord-66d3b94f4ad8442a8d56ccccb6221709
Source dataset
uspto-grants-2008_10
Patent number
US07432266B2

Reaction notes

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