Sodium Hydroxide → HCID 52920206, compound

HRID 1615391Notes

Reaction equation

HRID 1615391 reaction equation
C(OC[N:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([N:18]3[C:26]4[C:21](=[CH:22][CH:23]=[C:24]([C:27]5[CH:32]=[CH:31][CH:30]=[C:29]([NH2:33])[CH:28]=5)[CH:25]=4)[CH:20]=[CH:19]3)[C:12]=2[CH:11]=[CH:10]1)(=O)C(C)(C)C.[Cl:34][C:35]1[CH:43]=[CH:42][C:38]([C:39](O)=[O:40])=[CH:37][C:36]=1[C:44]([F:47])([F:46])[F:45].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[OH-].[Na+]>C1COCC1.O.C(OCC)(=O)C.CO>[N:14]1[C:13]2[NH:9][CH:10]=[CH:11][C:12]=2[C:17]([N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:27]4[CH:28]=[C:29]([NH:33][C:39](=[O:40])[C:38]5[CH:42]=[CH:43][C:35]([Cl:34])=[C:36]([C:44]([F:47])([F:45])[F:46])[CH:37]=5)[CH:30]=[CH:31][CH:32]=4)[CH:25]=3)[CH:20]=[CH:19]2)=[N:16][CH:15]=1

Participants

10

Reactant 5

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27738574-Chloro-3-(trifluoromethyl)benzoic acidHCID 67203834HCID 67203834, compound

Product 1

HCID 52920206HCID 52920206, compoundYield 80.9%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(4-(6-(3-Aminophenyl)-1H-indol-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (30 mg, 0.068 mmol), 4-chloro-3-(trifluoromethyl)benzoic acid (16.8 mg, 0.075 mmol) and HOBt (9.2 mg, 0.068 mmol) were dissolved in THF (1 mL). At room temperature, EDCI (39.2 mg, 0.20 mmol) was added. After adding 1 N NaOH (1 mL) and MeOH (1 mL), the mixture solution was stirred at room temperature for 2 hours. After adding ethyl acetate and water, the organic layer was separated. The aqueous layer was extracted with ethyl acetate and the combined organic layer was washed with brine, dried with magnesium sulfate, and concentrated under reduced pressure. Purification of the residue by column chromatography (silica gel, DCM:MeOH=20:1) yielded N-(3-(1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-indol-6-yl)phenyl)-4-chloro-3-(trifluoromethyl)benzamide (29 mg, 0.055 mmol) as white solid.

Workup

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layer was washed with brine
  4. dry with materialdried with magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the residue by column chromatography (silica gel, DCM:MeOH=20:1)

Sources & evidence

ORD record
ord-397d0bb9beb946679fc4796238ae1e79
Source dataset
uspto-grants-2014_07
Patent number
US08765749B2

Reaction notes

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