(R)-Methyl 6-(1-amino-4-methyl-1-oxopentan-2-ylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate → (R)-4-Methyl-2-(4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)pentanamide

HRID 711488Notes

Reaction equation

HRID 711488 reaction equation
[NH2:1][C:2](=[O:27])[C@H:3]([NH:8][C:9]1[CH:18]=[C:17]([C:19]#[N:20])[C:12]([C:13](OC)=[O:14])=[C:11]([C:21]2[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=2)[N:10]=1)[CH2:4][CH:5]([CH3:7])[CH3:6]>CO.CC(O)=O.[OH-].[Pd+2].[OH-]>[CH3:6][CH:5]([CH3:7])[CH2:4][C@@H:3]([NH:8][C:9]1[N:10]=[C:11]([C:21]2[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=2)[C:12]2[C:13](=[O:14])[NH:20][CH2:19][C:17]=2[CH:18]=1)[C:2]([NH2:1])=[O:27]

Participants

5

Reactant 1

HCID 67237475(R)-Methyl 6-(1-amino-4-methyl-1-oxopentan-2-ylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate

Product 1

HCID 58317577(R)-4-Methyl-2-(4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)pentanamideYield 54.2%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A mixture of (R)-methyl 6-(1-amino-4-methyl-1-oxopentan-2-ylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate (20.3 mg, 0.055 mmol) and palladium hydroxide (10 mg, 0.094 mmol) in MeOH (2 mL) and HOAc (2 mL) was stirred at RT for 3 h under a hydrogen atmosphere. The mixture was filtered to remove the catalyst and the filtrate was concentrated under reduced pressure. The residue was treated with saturated aq NaHCO3 (20 mL) and EtOAc (20 mL) for 12 h. The mixture was extracted with EtOAc (2×20 mL). The organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL), were dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (DM1020, EtOAc/MeOH=15/1-10/1) to give the title compound as a white solid (10.2 mg, 54%). 1H-NMR (DMSO-d6) δ ppm 0.88-0.95 (m, 6H), 1.52-1.60 (m, 2H), 1.73-1.76 (m, 1H), 3.88 (s, 3H), 4.21 (s, 2H), 4.48 (br s, 1H), 6.43 (s, 1H), 6.90 (s, 1H), 7.03 (br s, 1H), 7.42 (s, 1H), 8.01 (s, 1H), 8.41 (s, 1H), 8.92 (s, 1H). [M+H] calc'd for C17H23N6O2, 343. found, 343.

Workup

  1. filtrationThe mixture was filtered
  2. customto remove the catalyst
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionThe residue was treated with saturated aq NaHCO3 (20 mL) and EtOAc (20 mL) for 12 h
  5. extractionThe mixture was extracted with EtOAc (2×20 mL)
  6. washThe organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL)
  7. dry with materialwere dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customthe residue was purified by column chromatography (DM1020, EtOAc/MeOH=15/1-10/1)

Sources & evidence

ORD record
ord-a62053026cd54653acdb1943fe264119
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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