Sodium Hydroxide → HCID 9851483, compound

HRID 1266455Notes

Reaction equation

HRID 1266455 reaction equation
C([O:3][C:4]([CH:6]1[CH:10]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:39])[CH2:19][C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[CH3:36])=[O:28])=[C:22]([O:37][CH3:38])[CH:21]=3)=[CH:13][CH:12]=2)[CH2:9][N:8]([CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:7]1)=[O:5])C.[OH-].[Na+]>C(#N)C.C(O)C>[CH2:40]([N:8]1[CH2:9][CH:10]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:39])[CH2:19][C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[CH3:36])=[O:28])=[C:22]([O:37][CH3:38])[CH:21]=3)=[CH:13][CH:12]=2)[CH:6]([C:4]([OH:5])=[O:3])[CH2:7]1)[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 54324838HCID 54324838, compound

Product 1

HCID 9851483HCID 9851483, compoundYield 41.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Procedure

A stirred solution of 1-benzyl-4-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid ethyl ester (2.95 g, Reference Example 16) in a mixture of acetonitrile (150 mL) and ethanol (125 mL), at 50° C., was treated slowly with aqueous sodium hydroxide solution (0.46 mL, 30%). After stirring for 8 hours at room temperature and then gentle stirring for a week, the mixture was filtered. The solid was washed with dichloromethane (30 mL), then dried under reduced pressure (2.7 kPa) and then treated with water (200 mL). The mixture was acidified by addition of hydrochloric acid (3.5 mL, 1 M), then allowed to stand at room temperature for 15 hours, then treated with ethyl acetate (400 mL) and then filtered to give the title compound (1.16 g) as a white powder, m.p. 255° C. 1H-NMR [400 MHz, (CD3)2SO]: δ 2.27 (s, 3H); 2.45 to 2.60 (m, 1H); 2.80 to 3.00 (m, 4H); 3.49 (m, 1H); 3.57 (s, 2H); 3.58 and 3.68 (2 d, J=14 Hz, 2H); 3.90 (s, 3H); 6.85 (bd, J=8 Hz, 1H); 6.95 (bt, J=7 Hz, 1H); 7.02 (bs, 1H); 7.05 to 7.20 (m, 2H); 7.20 to 7.30 (m, 3H); 7.30 to 7.40 (m, 4H); 7.52 (bd, J=8 Hz, 2H); 7.82 (bd, J=8 Hz, 1H); 8.04 (d, J=8 Hz, 1H); 8.48 (bs, 1H); 8.59 (bs, 1H); 10.07 (bs, 1H). MS(LSIMS): 593[M+HI]+.

Workup

  1. stirringgentle stirring for a week
  2. filtrationthe mixture was filtered
  3. washThe solid was washed with dichloromethane (30 mL)
  4. customdried under reduced pressure (2.7 kPa)
  5. additiontreated with water (200 mL)
  6. additionThe mixture was acidified by addition of hydrochloric acid (3.5 mL, 1 M)
  7. waitto stand at room temperature for 15 hours
  8. additiontreated with ethyl acetate (400 mL)
  9. filtrationfiltered

Sources & evidence

ORD record
ord-d7a1075eb3c24025ac609087f6f25e50
Source dataset
uspto-grants-2003_04
Patent number
US06548533B2

Reaction notes

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