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

HRID 711486Notes

Reaction equation

HRID 711486 reaction equation
[NH2:1][C:2](=[O:32])[C@H:3]([NH:8][C:9]1[CH:18]=[C:17]([C:19]#[N:20])[C:12]([C:13]([O:15]C)=O)=[C:11]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:23]=2)[N:10]=1)[CH2:4][CH:5]([CH3:7])[CH3:6]>CO.CC(O)=O.[OH-].[OH-].[Pd+2]>[CH3:6][CH:5]([CH3:7])[CH2:4][C@@H:3]([NH:8][C:9]1[N:10]=[C:11]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([S:28]([CH3:31])(=[O:29])=[O:30])[CH:23]=2)[C:12]2[C:13](=[O:15])[NH:20][CH2:19][C:17]=2[CH:18]=1)[C:2]([NH2:1])=[O:32]

Participants

5

Reactant 1

HCID 67239420(R)-Methyl 6-(1-amino-4-methyl-1-oxopentan-2-ylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate

Product 1

HCID 53252440(R)-4-Methyl-2-(4-(3-(methylsulfonyl)phenylamino)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)pentanamideYield 27.4%

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-(3-(methylsulfonyl)phenylamino)nicotinate (73.2 mg, 0.159 mmol) and palladium hydroxide on carbon (23.2 mg, 0.165 mmol) in MeOH (6 mL) and HOAc (3 mL) was stirred at RT for 12 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 MeOH (20 mL). The resulting mixture was stirred at RT for 16 h and then concentrated under reduced pressure. The residue was treated with saturated aq NaHCO3 (30 mL) and extracted with EtOAc (2×50 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 recrystallized from EtOH to give the title compound as a white solid (18.8 mg, 27%). 1H-NMR (DMSO-d6) δ ppm 0.87-0.94 (m, 6H), 1.54-1.63 (m, 2H), 1.76 (br s, 1H), 3.32 (s, 3H), 4.24 (s, 2H), 4.50 (br s, 1H), 6.17 (s, 1H), 7.00-7.04 (m, 2H), 7.22 (br s, 1H), 7.47-7.57 (m, 2H), 8.01 (br s, 1H), 8.06 (s, 1H), 8.45 (br s, 1H), 9.23 (s, 1H). [M+H] calc'd for C20H26N5O4S, 432. found, 432.5.

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 MeOH (20 mL)
  5. stirringThe resulting mixture was stirred at RT for 16 h
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was treated with saturated aq NaHCO3 (30 mL)
  8. extractionextracted with EtOAc (2×50 mL)
  9. washThe organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL)
  10. dry with materialwere dried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated under reduced pressure
  13. customthe residue was recrystallized from EtOH

Sources & evidence

ORD record
ord-6e982e17a3254e9882617fa150f5b780
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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