Sodium Hydroxide → HCID 9959083, compound

HRID 1266451Notes

Reaction equation

HRID 1266451 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]([C:40](=[O:42])[CH3:41])[CH2:7]1)=[O:5])C.[OH-].[Na+]>C(O)C>[C: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)(=[O:42])[CH3:41]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 54035024HCID 54035024, compound

Product 1

HCID 9959083HCID 9959083, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
23 °C

Procedure

A solution of 1-acetyl-4-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid ethyl ester (1.62 g, Reference Example 1) in anhydrous ethanol (60 ml) was treated dropwise with sodium hydroxide solution (48 ml, 0.1 M). After stirring for 15 hours at 23° C. the mixture was evaporated (40° C. and 2.7 kPa). The residue was diluted with distilled water (200 ml), then cooled to 5° C. and then the pH of the mixture was adjusted to 2 by dropwise addition of hydrochloric acid (1N) resulting in the precipitation of a white solid. After stirring at 23° C. for 15 hours the mixture was filtered. The white solid was dried under reduced pressure (2.7 kPa) then triturated with ether affording the title compound (1 g) as a white solid, m.p. 242° C. 1H-NMR [600 MHz, (CD3)2SO]: δ 1.95 and 1.98 (2 s, 3H); 2.25 (s, 3H); 3.10 to 3.95 (m, 6H); 3.58 (s, 2H); 3.89 (s, 3H); 6.85 (bd, J=8 Hz, 1H); 6.95 (t, J=7.5 Hz, 1H); 7.02 (bs, 1H); 7.13 (t, J=7.5 Hz, 1H); 7.17 (d, J=7.5 Hz, 1H); 7.25 and 7.28 (2 d, J=8 Hz, 2H); 7.50 to 7.60 (m, 2H); 7.80 (d, J=7.5 Hz, 1H); 8.04 (d, J=8 Hz, 1H); 8.48 (s, 1H); 8.59 (s, 1H). MS [FAB (meta-nitrobenzylalcohol)]: 545 [M+H]+.

Workup

  1. customwas evaporated (40° C. and 2.7 kPa)
  2. additionThe residue was diluted with distilled water (200 ml)
  3. temperaturecooled to 5° C.
  4. additionthe pH of the mixture was adjusted to 2 by dropwise addition of hydrochloric acid (1N)
  5. customresulting in the precipitation of a white solid
  6. stirringAfter stirring at 23° C. for 15 hours the mixture
  7. filtrationwas filtered
  8. customThe white solid was dried under reduced pressure (2.7 kPa)
  9. customthen triturated with ether affording the title compound (1 g) as a white solid, m.p. 242° C

Sources & evidence

ORD record
ord-4f21d8203a32437d8facfe10f37b44e1
Source dataset
uspto-grants-2003_04
Patent number
US06548533B2

Reaction notes

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