Trifluoroacetic acid → Trifluoroacetic acid

HRID 1364968Notes

Reaction equation

HRID 1364968 reaction equation
Br[CH2:2][C:3]([C:5]1[N:6]([CH2:24][C:25]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[O:26])[C:7]2[C:12]([C:13]=1[CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)=[CH:11][CH:10]=[C:9]([C:20]([O:22]C)=[O:21])[CH:8]=2)=O.[C:33]([NH:37][C:38]([NH2:40])=[S:39])([CH3:36])([CH3:35])[CH3:34].[OH-].[Na+].[C:43]([OH:49])([C:45]([F:48])([F:47])[F:46])=[O:44]>CS(C)=O>[C:33]([NH:37][C:38]1[S:39][CH:2]=[C:3]([C:5]2[N:6]([CH2:24][C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[O:26])[C:7]3[C:12]([C:13]=2[CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]2)=[CH:11][CH:10]=[C:9]([C:20]([OH:22])=[O:21])[CH:8]=3)[N:40]=1)([CH3:36])([CH3:35])[CH3:34].[C:43]([OH:49])([C:45]([F:48])([F:47])[F:46])=[O:44]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14798Sodium Hydroxide2×HCID 737374N-(tert-Butyl)thioureaHCID 21105283Methyl 2-(2-bromo-ethanoyl)-3-cyclohexyl-1-(2-morpholin-4yl-2-oxo-ethyl)-1H-indole-6carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 211052522-(2-Tert-butylamino-thiazol-4-yl)-3-cyclohexyl-1-(2-morpholin-4-yl-2-oxo-ethyl)-1h-indole-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

The bromomethylketone of example 11 (39.6 mg, 0.078 mmol, 1 equiv.) was dissolved in DMSO (1 mL) and N-tertbutylthiourea (12.4 mg, 0.094 mmol, 1.2 equiv.) was added. The mixture was stirred for 2 h at room temperature. 10 N NaOH (24 μL) was added and after stirring for 4 h at room temperature, another portion of 10 N NaOH (24 μL) was added and the mixture stirred 24 h at room temperature to complete the hydrolysis. The reaction mixture was then neutralized by addition of TFA and the title product of example 12 isolated directly from the reaction mixture by preparative HPLC as a white amorphous TFA salt (21 mg).

Workup

  1. stirringafter stirring for 4 h at room temperature
  2. stirringthe mixture stirred 24 h at room temperature
  3. customthe hydrolysis

Sources & evidence

ORD record
ord-9927000c0d364b42b1a3ff6f8941cd86
Source dataset
uspto-grants-2011_02
Patent number
US07888363B2

Reaction notes

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