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 2092787ノート

反応式

HRID 2092787 の反応式
[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]

参加物

5

反応物 1

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 9942167Palladium hydroxide触媒HCID 176Acetic Acid溶媒HCID 887Methanol溶媒

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-ec10fdc648d043e6a6ae6887a7e39db0
出典データセット
uspto-grants-2013_05
特許番号
US08440689B2

反応ノート

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