Acetic Acid → 5-(3-{[[2-(tert-Butoxycarbonyl-methyl-amino)-ethyl]-(3-fluoro-benzyl)-amino]-methyl}-4-fluoro-phenyl)-indazole-1-carboxylic acid tert-butyl ester

HRID 1864794Notes

Reaction equation

HRID 1864794 reaction equation
C(O[BH-](O[C:11](=O)[CH3:12])OC(=O)C)(=O)C.[Na+].[C:15](O)(=O)C.[C:19]([O:23][C:24]([N:26]1[C:34]2[C:29](=[CH:30][C:31]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[C:37]([CH2:42][NH:43][CH2:44][CH2:45][N:46]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH3:47])[CH:36]=3)=[CH:32][CH:33]=2)[CH:28]=[N:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].[F:55][C:56]1[CH:63]=CC(C=O)=[CH:58][CH:57]=1>ClC(Cl)C.O>[C:19]([O:23][C:24]([N:26]1[C:34]2[C:29](=[CH:30][C:31]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[C:37]([CH2:42][N:43]([CH2:44][CH2:45][N:46]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH3:47])[CH2:15][C:11]4[CH:12]=[CH:58][CH:57]=[C:56]([F:55])[CH:63]=4)[CH:36]=3)=[CH:32][CH:33]=2)[CH:28]=[N:27]1)=[O:25])([CH3:21])([CH3:22])[CH3:20]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 680234-FluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 687486135-(3-{[2-(tert-Butoxycarbonyl-methyl-amino)-ethylamino]-methyl}-4-fluoro-phenyl)-indazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 687474165-(3-{[[2-(tert-Butoxycarbonyl-methyl-amino)-ethyl]-(3-fluoro-benzyl)-amino]-methyl}-4-fluoro-phenyl)-indazole-1-carboxylic acid tert-butyl esterYield 74.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (254 mg, 1.2 mmol) and acetic acid (48 mg, 0.8 mmol) were added to a mixture of 5-(3-{[2-(tert-butoxycarbonyl-methyl-amino)-ethylamino]-methyl}-4-fluoro-phenyl)-indazole-1-carboxylic acid tert-butyl ester (400 mg, 0.8 mmol) and 4-fluorobenzaldehyde (99 mg, 0.8 mmol) in 15 mL of dichloroethane. The mixture was stirred at ambient temperature for 80 h, and then it was diluted with water, the layers were separated and the aqueous phase was extracted with dichloromethane. The combined organic layers were washed with sequentially with water, saturated sodium bicarbonate solution and water, dried over magnesium sulfate, filtered and concentrated to leave the crude product. Chromatography (elution with ethyl acetate/pentane) provided 360 mg of product. LC/MS: Retention time, 4.10 min; (M+H)=607.

Workup

  1. customthe layers were separated
  2. extractionthe aqueous phase was extracted with dichloromethane
  3. washThe combined organic layers were washed with sequentially with water, saturated sodium bicarbonate solution and water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto leave the crude product
  8. washChromatography (elution with ethyl acetate/pentane)

Sources & evidence

ORD record
ord-8e905ddf8d0c4ab4b51cc3dea0f0bf46
Source dataset
uspto-grants-2009_12
Patent number
US07625889B2

Reaction notes

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