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 2088632Notes

Reaction equation

HRID 2088632 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. additionwas added in four aliquots over 15 minutes
  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-79613f50aed44ef2971c0f08234728f3
Source dataset
uspto-grants-2013_05
Patent number
US08435988B2

Reaction notes

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