Sodium Hydroxide → HCID 9873611, compound

HRID 1266454Notes

Reaction equation

HRID 1266454 reaction equation
C([O:3][C:4]([CH:6]1[CH2:10][CH2:9][N:8]([C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:7]1[C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:47])[CH2:27][C:28]2[CH:33]=[CH:32][C:31]([NH:34][C:35]([NH:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[CH3:44])=[O:36])=[C:30]([O:45][CH3:46])[CH:29]=2)=[CH:21][CH:20]=1)=[O:5])C.[OH-].[Na+]>C(O)C.C(#N)C>[C:11]([N:8]1[CH2:9][CH2:10][CH:6]([C:4]([OH:5])=[O:3])[CH:7]1[C:19]1[CH:20]=[CH:21][C:22]([NH:25][C:26](=[O:47])[CH2:27][C:28]2[CH:33]=[CH:32][C:31]([NH:34][C:35]([NH:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[CH3:44])=[O:36])=[C:30]([O:45][CH3:46])[CH:29]=2)=[CH:23][CH:24]=1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 69833704HCID 69833704, compound

Product 1

HCID 9873611HCID 9873611, compoundYield 42.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
5 °C

Procedure

A stirred solution of 1-benzoyl-2-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid ethyl ester (0.33 g, Reference Example 13) in a mixture of ethanol (4 ml) and acetonitrile (40 ml), at 20° C., was treated dropwise with aqueous sodium hydroxide solution (0. 15 ml, 10 N). After stirring for 6 days the mixture was filtered and the insoluble light brown solid was triturated twice with acetonitrile (5 ml), then twice with dichloromethane (2.5 ml) and then dried. The solid was dissolved in water (30 ml) and filtered. The filtrate was cooled to 5° C. and the pH of the mixture adjusted to 2 by dropwise addition of hydrochloric acid (1.2 ml, 1N). The resulting white precipitate was filtered then washed three times with water (5 ml), then twice with diisopropyl ether (10 ml) and then dried under reduced pressure (40° C. and 2.7 kPa) to afford the title compound (0.134 g) as an off-white powder, m.p. 155° C. (with decomposition). 1H-NMR [500 MHz, (CD3)2SO at 383° K.]: δ 2.15 (m, 2H); 2.27 (s, 3H); 2.96 (m, 1H); 3.59 (s, 2H); 3.75 (m, 2H); 3.89 (s, 3H); 5.32 (m, 1H); 6.87 (bd, J=8 Hz, 1H); 6.98 (t, J=7.5 Hz, 1H); 7.02 (d, J=1.5 Hz, 1H); 7.10 to 7.25 (m, 4H); 7.30 to 7.45 (m, 5H); 7.52 (d, J=8.5 Hz, 2H); 7.67 (d, J=8 Hz, 1H); 7.99 (d, J=8 Hz, 1H); 8.15 (bs, 1H); 8.21 (bs, 1H); 9.55 (bs, 1H). MS(ES): 629 [M+Na]+.

Workup

  1. filtrationwas filtered
  2. customthe insoluble light brown solid was triturated twice with acetonitrile (5 ml)
  3. dry with materialtwice with dichloromethane (2.5 ml) and then dried
  4. dissolutionThe solid was dissolved in water (30 ml)
  5. filtrationfiltered
  6. additionthe pH of the mixture adjusted to 2 by dropwise addition of hydrochloric acid (1.2 ml, 1N)
  7. filtrationThe resulting white precipitate was filtered
  8. washthen washed three times with water (5 ml)
  9. dry with materialtwice with diisopropyl ether (10 ml) and then dried under reduced pressure (40° C. and 2.7 kPa)

Sources & evidence

ORD record
ord-bf5b7b55e3bf4c44a0f0656a600d77e1
Source dataset
uspto-grants-2003_04
Patent number
US06548533B2

Reaction notes

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