1,1'-Carbonyldiimidazole → Saprisartan

HRID 1729503Notes

Reaction equation

HRID 1729503 reaction equation
C(N1C=CN=C1)([N:3]1C=CN=C1)=O.[Br:13][C:14]1[C:18]2[CH:19]=[C:20]([CH2:23][N:24]3[C:28]([C:29]([OH:31])=O)=[C:27]([CH:32]4[CH2:34][CH2:33]4)[N:26]=[C:25]3[CH2:35][CH3:36])[CH:21]=[CH:22][C:17]=2[O:16][C:15]=1[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[NH:43][S:44]([C:47]([F:50])([F:49])[F:48])(=[O:46])=[O:45]>C1COCC1>[Br:13][C:14]1[C:18]2[CH:19]=[C:20]([CH2:23][N:24]3[C:28]([C:29]([NH2:3])=[O:31])=[C:27]([CH:32]4[CH2:33][CH2:34]4)[N:26]=[C:25]3[CH2:35][CH3:36])[CH:21]=[CH:22][C:17]=2[O:16][C:15]=1[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[NH:43][S:44]([C:47]([F:49])([F:48])[F:50])(=[O:45])=[O:46]

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 10077492HCID 10077492, compound

Product 1

HCID 60921SaprisartanYield 100.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1'-Carbonyldiimidazole (14.3 g) was added in one portion to a solution of the product of Example 5 (18 g) in dry THF (600 ml) at room temperature under nitrogen. The mixture was stirred for 16 h, then ammonia was bubbled through the solution for 30 mins, and the mixture then stirred for 5 h. Ammonia was again bubbled through the reaction mixture for 30 mins, and the solution stirred for a further 16 h. The reaction mixture was diluted with ethyl acetate (1 liter) and cooled in an ice-bath. Cold dilute hydrochloric acid (0.25M ca. 1 liter) was added dropwise to the vigorously stirred reaction mixture until pH6 was achieved. The aqueous phase was separated and extracted further with ethyl acetate (3×500 ml). The combined organic extracts were washed with brine (2×800 ml) and dried. The solvent was evaporated to give a colourless foam (18 g) which was triturated under ether (250 ml) and filtered to give a colourless amorphous solid (13.8 g), m.p. 155.6°-159.2°.

Workup

  1. customammonia was bubbled through the solution for 30 mins
  2. stirringthe mixture then stirred for 5 h
  3. customAmmonia was again bubbled through the reaction mixture for 30 mins
  4. stirringthe solution stirred for a further 16 h
  5. additionThe reaction mixture was diluted with ethyl acetate (1 liter)
  6. temperaturecooled in an ice-bath
  7. additionCold dilute hydrochloric acid (0.25M ca. 1 liter) was added dropwise to the vigorously stirred reaction mixture until pH6
  8. customThe aqueous phase was separated
  9. extractionextracted further with ethyl acetate (3×500 ml)
  10. washThe combined organic extracts were washed with brine (2×800 ml)
  11. customdried
  12. customThe solvent was evaporated

Sources & evidence

ORD record
ord-5e240aa497994be5b098eb8936be4df1
Source dataset
uspto-grants-1994_07
Patent number
US05332831

Reaction notes

Loading…