(1-{1-[6-(3,4-Difluoro-phenoxy)-4-(tetrahydro-pyran-4-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester → N-{1-[6-(3,4-Difluoro-phenoxy)-4-pyrimidin-2-yl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propyl}-2-methylamino-propionamide

HRID 1965177Notes

Reaction equation

HRID 1965177 reaction equation
C(O[C:9](=O)[N:10]([CH:12]([C:14](=[O:46])[NH:15][CH:16]([C:21]([N:23]1[CH2:27][CH2:26][CH:25]2[N:28]([CH:40]3CCOCC3)[CH2:29][CH:30]([O:31][C:32]3[CH:37]=[CH:36][C:35]([F:38])=[C:34]([F:39])[CH:33]=3)[CH:24]12)=[O:22])[C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13])C)C1C=CC=CC=1>CO>[F:39][C:34]1[CH:33]=[C:32]([CH:37]=[CH:36][C:35]=1[F:38])[O:31][CH:30]1[CH:24]2[N:23]([C:21]([CH:16]([NH:15][C:14](=[O:46])[CH:12]([NH:10][CH3:9])[CH3:13])[C:17]([CH3:19])([CH3:20])[CH3:18])=[O:22])[CH2:27][CH2:26][CH:25]2[N:28]([C:40]2[N:28]=[CH:29][CH:30]=[CH:24][N:23]=2)[CH2:29]1

Participants

3

Reactant 1

HCID 67608273(1-{1-[6-(3,4-Difluoro-phenoxy)-4-(tetrahydro-pyran-4-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester

Product 1

HCID 67609539N-{1-[6-(3,4-Difluoro-phenoxy)-4-pyrimidin-2-yl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propyl}-2-methylamino-propionamideYield 64.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The Cbz-protected intermediate 31 (180 mg, 0.27 mmol) was stirred vigorously with 10% Pd-on-carbon (wet, 100 mg, 0.09 mmol) in MeOH (20 mL) under 1 atm H2. After 4 h, the catalyst was removed by filtration with an Acrodisc® 0.45 μm nylon membrane syringe filter and the solvent was removed in vacuo. The crude product was purified by reverse-phase HPLC (2″ Dynamax® C18, 10-55% ACN/water containing 0.1% HOAc over 20 min; Flow: 40 mL/min) to afford 45 mg of 32 (32%, 3 steps) as a flocculent, white solid following lyophilization.

Workup

  1. customthe catalyst was removed by filtration with an Acrodisc® 0.45 μm nylon membrane syringe
  2. filtrationfilter
  3. customthe solvent was removed in vacuo
  4. customThe crude product was purified by reverse-phase HPLC (2″ Dynamax® C18, 10-55% ACN/water containing 0.1% HOAc over 20 min

Sources & evidence

ORD record
ord-06a9ee171b974420bb58c132bd7bf4e9
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

Loading…