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 44568Notes

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

Conditions

Temperature: 6 °C

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 6° 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

temperaturecooled (1 C/min) to 20 C
stirringstirred at 20 C for 8 hours
customThe solids were isolated by vacuum filtration
customdried at 60 C under vacuum for 5 hours

Sources & evidence

ORD record: ord-c64fce19c9ae4dd1ae929f7848b99444
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541411B2

Reaction notes

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