Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclopentylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate → tert-Butyl (1S,2R)-2-(4-(3-(methylsulfonyl)phenylamino)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclopentylcarbamate

HRID 516019Notes

Reaction equation

HRID 516019 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[NH:14][C:15]1[CH:24]=[C:23]([C:25]#[N:26])[C:18]([C:19](OC)=[O:20])=[C:17]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([S:34]([CH3:37])(=[O:36])=[O:35])[CH:29]=2)[N:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.CC(O)=O.[OH-].[OH-].[Pd+2]>[CH3:37][S:34]([C:30]1[CH:29]=[C:28]([NH:27][C:17]2[C:18]3[C:19](=[O:20])[NH:26][CH2:25][C:23]=3[CH:24]=[C:15]([NH:14][C@@H:10]3[CH2:11][CH2:12][CH2:13][C@@H:9]3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[N:16]=2)[CH:33]=[CH:32][CH:31]=1)(=[O:35])=[O:36]

Participants

5

Reactant 1

HCID 67238760Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclopentylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate

Product 1

HCID 86654717tert-Butyl (1S,2R)-2-(4-(3-(methylsulfonyl)phenylamino)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclopentylcarbamateYield 34.9%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A mixture of methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclopentylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate (141.1 mg, 0.266 mmol) and palladium hydroxide on carbon (43.2 mg, 0.308 mmol) in MeOH (10 mL) and HOAc (10 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 mixture was stirred at RT for 6 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 purified by column chromatography (DM1020, EtOAc) to give the desired product (46.5 mg). The product was washed with IPE/EtOAc to give the title compound as a pale brown solid (34.7 mg, 26%).

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 mixture was stirred at RT for 6 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 purified by column chromatography (DM1020, EtOAc)

Sources & evidence

ORD record
ord-b014fdea9c5148e3b859e8a3b30b11a8
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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