Hydrochloric Acid → HCID 19867557, compound

HRID 1198975Notes

Reaction equation

HRID 1198975 reaction equation
[H-].[Na+].[CH:3]1([CH2:8][NH:9][C:10]([C:12]2[CH:20]=[C:19]3[C:15]([C:16]([CH2:34][OH:35])=[N:17][N:18]3[CH2:21][C:22]3[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][C:23]=3[O:32][CH3:33])=[CH:14][CH:13]=2)=[O:11])[CH2:7][CH2:6][CH2:5][CH2:4]1.[CH3:36][N:37]([CH3:41])[C:38](Cl)=[O:39].Cl>O1CCCC1.CN(C)C=O>[CH:3]1([CH2:8][NH:9][C:10]([C:12]2[CH:20]=[C:19]3[C:15]([C:16]([CH2:34][O:35][C:38](=[O:39])[N:37]([CH3:41])[CH3:36])=[N:17][N:18]3[CH2:21][C:22]3[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][C:23]=3[O:32][CH3:33])=[CH:14][CH:13]=2)=[O:11])[CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6598Dimethylcarbamoyl ChlorideHCID 24758Sodium hydrideHCID 19867556HCID 19867556, compound

Product 1

HCID 19867557HCID 19867557, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 60% sodium hydride dispersion (13 mg) (petroleum ether washed) in tetrahydrofuran (1 ml) at 0° was added a solution of methyl 4-[6-(N-cyclopentylmethylcarbamoyl)-3-hydroxymethylindazol-1-ylmethyl]-3-methoxybenzoate (151 mg) in 7:1 dimethylformamide:tetrahydrofuran (8 ml). After stirring for 45 minutes, dimethylcarbamoyl chloride (0.033 ml) was added. The reaction was stirred for 15 minutes and was allowed to warm to room temperature. After 3 hours, 1N hydrochloric acid was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried (MgSO4). Evaporation and flash chromatography over 15 g silica gel, eluting with 2:8 ethyl acetate:methylene chloride (50 ml) and 4:6 ethyl acetate:methylene chloride, afforded methyl 4-[6-(N-cyclopentylmethylcarbamoyl)-3-(dimehylcarbamoyloxymethyl)indazol-1-ylmethyl]-3-methoxybenzoate as a colorless solid (40 mg, 23%); mass spectrum (chemical ionization) 523 (M+H). NOTE: Still further Examples of compounds of the invention are provided by the benzoic acid starting materials for formula I (M=CO2H) described in connection with Examples 6, 8 and 9.

Workup

  1. stirringThe reaction was stirred for 15 minutes
  2. waitAfter 3 hours
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. customEvaporation and flash chromatography over 15 g silica gel
  7. washeluting with 2:8 ethyl acetate

Sources & evidence

ORD record
ord-612524637c5d4182b958512c212c7b4e
Source dataset
uspto-grants-1990_02
Patent number
US04898863

Reaction notes

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