Acetic Acid → 5-{4-Fluoro-3-[(3-pyrrolidin-1-yl-propylamino)-methyl]-phenyl}-indazole-1-carboxylic acid tert-butyl ester

HRID 1864799Notes

Reaction equation

HRID 1864799 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]([O:19][C:20]([N:22]1[C:30]2[C:25](=[CH:26][C:27]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[C:33]([CH:38]=O)[CH:32]=3)=[CH:28][CH:29]=2)[CH:24]=[N:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[NH2:40][CH2:41][CH2:42][CH2:43][N:44]1[CH2:48][CH2:47][CH2:46][CH2:45]1.C(O)(=O)C>ClC(Cl)C.ClCCl>[C:15]([O:19][C:20]([N:22]1[C:30]2[C:25](=[CH:26][C:27]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[C:33]([CH2:38][NH:40][CH2:41][CH2:42][CH2:43][N:44]4[CH2:48][CH2:47][CH2:46][CH2:45]4)[CH:32]=3)=[CH:28][CH:29]=2)[CH:24]=[N:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 316701-PyrrolidinepropanamineHCID 5049666Sodium triacetoxyborohydrideHCID 866164695-(4-Fluoro-3-formylphenyl)-indazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 687505725-{4-Fluoro-3-[(3-pyrrolidin-1-yl-propylamino)-methyl]-phenyl}-indazole-1-carboxylic acid tert-butyl esterYield 99.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (190 mg, 0.88 mmol) was added to a mixture of 5-(4-fluoro-3-formylphenyl)-indazole-1-carboxylic acid tert-butyl ester (100 mg, 0.29 mmol) and N-(3-aminopropyl)pyrrolidine (74 mg, 0.59 mmol) and acetic acid (105 mg, 1.8 mmol) in dichloroethane. The mixture was stirred at ambient temperature overnight, and then it was diluted with dichloromethane and washed with 1 M sodium carbonate solution. The layers were separated and the aqueous phase extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated to leave the crude product. Chromatography (elution with methanol/dichloromethane) provided 130 mg of product. LC/MS: Retention time, 1.98 min; (M+H)=453.

Workup

  1. washwashed with 1 M sodium carbonate solution
  2. customThe layers were separated
  3. extractionthe aqueous phase extracted with dichloromethane
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto leave the crude product
  8. washChromatography (elution with methanol/dichloromethane)

Sources & evidence

ORD record
ord-27e26f2df4c541639c419bc5f2e8911b
Source dataset
uspto-grants-2009_12
Patent number
US07625889B2

Reaction notes

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