Tris(hydroxymethyl)aminomethane → 2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylic acid 2-amino-2-(hydroxymethyl)-1,3-propanediol

HRID 539246Notes

Reaction equation

HRID 539246 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[C:9]=2[CH3:18])[C:5]2[CH:19]=[C:20]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[CH:21]=[C:22]([C:23]([OH:25])=[O:24])[C:4]=2[N:3]=1.[NH2:32][C:33]([CH2:38][OH:39])([CH2:36][OH:37])[CH2:34][OH:35]>CO>[NH2:32][C:33]([CH2:38][OH:39])([CH2:36][OH:37])[CH2:34][OH:35].[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:16])([F:15])[F:17])[C:9]=2[CH3:18])[C:5]2[CH:19]=[C:20]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[CH:21]=[C:22]([C:23]([OH:25])=[O:24])[C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 6503Tris(hydroxymethyl)aminomethane2×HCID 56949517Gsk-2636771

Product 1

HCID 669766662-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylic acid 2-amino-2-(hydroxymethyl)-1,3-propanediol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To the 2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylic acid (353.0 mg), methanol (14.0 mL) was added. The slurry was heated to 60 C. and tromethamine (3.0 M solution in water, 1.0 equivalent) was added in four aliquots over 15 minutes followed by the addition of crystalline seeds of crystalline tromethamine salt from batch 1. The slurry was stirred at 60 C for 3 hours, cooled (1 C/min) to 20 C, and stirred at 20 C for 8 hours. The solids were isolated by vacuum filtration, dried at 60 C under vacuum for 5 hours. The yield of the tromethamine salt was 401.5 mg (˜88.9% yield).

Workup

  1. temperatureThe slurry was heated to 60 C
  2. temperaturecooled (1 C/min) to 20 C
  3. stirringstirred at 20 C for 8 hours
  4. customThe solids were isolated by vacuum filtration
  5. customdried at 60 C under vacuum for 5 hours

Sources & evidence

ORD record
ord-4a37303b0b4a43bd9d2d9a308f473872
Source dataset
uspto-grants-2014_10
Patent number
US08865912B2

Reaction notes

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