Lithium Hydroxide → 1-{[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl}-2-[(1-cyclopropylpiperidin-4-yl)carbamoyl]-1H-benzimidazole-5-carboxylic acid

HRID 18578Notes

Reaction equation

HRID 18578 reaction equation
C[O:2][C:3]([C:5]1[CH:37]=[CH:36][C:8]2[N:9]([CH2:24][C:25]3[CH:29]=[C:28]([C:30]4[S:31][C:32]([Cl:35])=[CH:33][CH:34]=4)[O:27][N:26]=3)[C:10]([C:12](=[O:23])[NH:13][CH:14]3[CH2:19][CH2:18][N:17]([CH:20]4[CH2:22][CH2:21]4)[CH2:16][CH2:15]3)=[N:11][C:7]=2[CH:6]=1)=[O:4].[Li+].[OH-]>>[Cl:35][C:32]1[S:31][C:30]([C:28]2[O:27][N:26]=[C:25]([CH2:24][N:9]3[C:8]4[CH:36]=[CH:37][C:5]([C:3]([OH:4])=[O:2])=[CH:6][C:7]=4[N:11]=[C:10]3[C:12](=[O:23])[NH:13][CH:14]3[CH2:19][CH2:18][N:17]([CH:20]4[CH2:21][CH2:22]4)[CH2:16][CH2:15]3)[CH:29]=2)=[CH:34][CH:33]=1

Participants

3

Reactant 2

HCID 3939Lithium HydroxideHCID 68616248HCID 68616248, compound

Product 1

HCID 533163871-{[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl}-2-[(1-cyclopropylpiperidin-4-yl)carbamoyl]-1H-benzimidazole-5-carboxylic acid

Conditions

Temperature
60 °C

Procedure

7.84 g (14.52 mmol) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid methyl ester were dissolved in 400 mL MEOH. 72.59 mL (72.59 mmol) of a 1 M aqueous LiOH-solution were added and the resulting mixture was stirred for 7 h at 60° C. The solution was concentrated to a volume of approx. 200 mL and acidified by the addition of a 4 M aqueous HCl-solution until pH≈1 was reached. After 30 minutes the resulting precipitate was filtered off and washed several times with cold MeOH. Recrystallization from MEOH gave pure 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid in form of a colorless, crystalline solid. The title compound was obtained as its monohydrochloride.

Workup

  1. concentrationThe solution was concentrated to a volume of approx. 200 mL
  2. additionacidified by the addition of a 4 M aqueous HCl-solution until pH≈1
  3. filtrationAfter 30 minutes the resulting precipitate was filtered off
  4. washwashed several times with cold MeOH
  5. customRecrystallization from MEOH

Sources & evidence

ORD record
ord-5e2b10596ceb47b9add72706a817b750
Source dataset
uspto-grants-2010_06
Patent number
US07741341B2

Reaction notes

Loading…