(1-{1-Cyclohexyl-2-[4-cyclopropanecarbonyl-6-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethylcarbamoyl}-ethyl) methyl-carbamic benzyl ester → 4-[2-Cyclohexyl-2-(2-methylamino-propionylamino)-acetyl]-1-cyclopropanecarbonyl-octahydro-pyrrolo[3,2-b]pyrrole-3-carboxylic acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide

HRID 446985Notes

Reaction equation

HRID 446985 reaction equation
C(O[C:9](=O)[N:10]([CH:12]([C:14](=[O:51])[NH:15][CH:16]([CH:45]1[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1)[C:17]([N:19]1[CH2:23][CH2:22][CH:21]2[N:24]([C:40]([CH:42]3[CH2:44][CH2:43]3)=[O:41])[CH2:25][CH:26]([C:27](=[O:39])[NH:28][CH:29]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:32][CH2:31][CH2:30]3)[CH:20]12)=[O:18])[CH3:13])C)C1C=CC=CC=1>CO.[Pd]>[CH:29]1([NH:28][C:27]([CH:26]2[CH2:25][N:24]([C:40]([CH:42]3[CH2:44][CH2:43]3)=[O:41])[CH:21]3[CH2:22][CH2:23][N:19]([C:17](=[O:18])[CH:16]([CH:45]4[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50]4)[NH:15][C:14](=[O:51])[CH:12]([NH:10][CH3:9])[CH3:13])[CH:20]23)=[O:39])[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:32][CH2:31][CH2:30]1

Participants

4

Reactant 1

HCID 67282642(1-{1-Cyclohexyl-2-[4-cyclopropanecarbonyl-6-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethylcarbamoyl}-ethyl) methyl-carbamic benzyl ester

Product 1

HCID 672814114-[2-Cyclohexyl-2-(2-methylamino-propionylamino)-acetyl]-1-cyclopropanecarbonyl-octahydro-pyrrolo[3,2-b]pyrrole-3-carboxylic acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-amideYield 33.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of 48 (450 mg, 0.63 mmol) and 10% palladium-on-carbon (wet, 90 mg) in MeOH (15 mL) was shaken at 50 psi under a H2 atmosphere. After 1.5 h, the mixture was filtered through a 0.45 μM filtering disc, washed with MeOH and concentrated. Purification by reverse-phase HPLC (2″ Dynamax® C18, 10-70% ACN in H2O with 0.1% HOAc over 30 min) afforded 49 (123 mg) as a white flocculent solid following lyophilization of the purified fractions.

Workup

  1. filtrationthe mixture was filtered through a 0.45 μM
  2. filtrationfiltering disc
  3. washwashed with MeOH
  4. concentrationconcentrated
  5. customPurification by reverse-phase HPLC (2″ Dynamax® C18, 10-70% ACN in H2O with 0.1% HOAc over 30 min)

Sources & evidence

ORD record
ord-88a492ca45dd470488302d79e2e93b72
Source dataset
uspto-grants-2013_07
Patent number
US08481495B2

Reaction notes

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