Methanol → 6-((1R,2S)-2-Aminocyclohexylamino)-4-(3-(methylsulfonyl)phenylamino)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

HRID 711481ノート

反応式

HRID 711481 の反応式
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[CH:18]=[C:17]([C:19]#[N:20])[C:12](C(OC)=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.[CH3:32][OH:33]>[Pd].Cl>[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[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:30])=[O:29])[CH:23]=2)[C:12]2[C:32](=[O:33])[NH:20][CH2:19][C:17]=2[CH:18]=1

参加物

5

反応物 2

HCID 887MethanolHCID 67237982Methyl 6-((1R,2S)-2-aminocyclohexylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate

生成物 1

HCID 532524386-((1R,2S)-2-Aminocyclohexylamino)-4-(3-(methylsulfonyl)phenylamino)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one収率 34%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 313Hydrochloric Acid溶媒

実験手順

A mixture of methyl 6-((1R,2S)-2-aminocyclohexylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate (117.3 mg, 0.264 mmol) and palladium on carbon (23.6 mg, 0.222 mmol) in MeOH (4 mL) and 1N HCl (4 mL) was stirred at RT for 16 h under a hydrogen atmosphere. The mixture was filtered to remove the catalyst and the filtrate was treated with saturated aq NaHCO3 (20 mL) and stirred at RT for 20 h. The mixture was concentrated under reduced pressure and the residue was extracted with EtOAc/THF (2/1, 2×30 mL). The organic layers were washed with saturated aq NaHCO3 (15 mL), water (15 mL) and brine (15 mL), were dried over anhydrous Na2SO4, and then filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (DM1020, EtOAc/MeOH=20/1) to give the desired product (37.2 mg, 34%). The product was recrystallized from EtOH to give the title compound as a colorless solid (13.2 mg, 12%). 1H-NMR (DMSO-d6) δ ppm 1.31-1.41 (m, 4H), 1.55-1.68 (m, 6H), 3.05 (s, 1H), 3.21 (s, 3H), 4.08 (s, 1H), 4.23 (s, 2H), 6.17 (s, 1H), 6.78-6.79 (m, 1H), 7.46-7.47 (m, 1H), 7.53-7.56 (m, 1H), 7.96-7.99 (m, 2H), 8.49 (s, 1H), 9.18 (s, 1H).

後処理

  1. filtrationThe mixture was filtered
  2. customto remove the catalyst
  3. additionthe filtrate was treated with saturated aq NaHCO3 (20 mL)
  4. stirringstirred at RT for 20 h
  5. concentrationThe mixture was concentrated under reduced pressure
  6. extractionthe residue was extracted with EtOAc/THF (2/1, 2×30 mL)
  7. washThe organic layers were washed with saturated aq NaHCO3 (15 mL), water (15 mL) and brine (15 mL)
  8. dry with materialwere dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe residue was purified by column chromatography (DM1020, EtOAc/MeOH=20/1)

出典と根拠

ORDレコード
ord-213695575a5a492e91db0877a1cecac4
出典データセット
uspto-grants-2015_11
特許番号
US09181255B2

反応ノート

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