Trifluoroacetic acid → (+/-)-tert-butyl (1R,2S,3S,5R)-5-(3-aminopyridin-4-yl)-2-cyano-3-methylcyclohexylcarbamate

HRID 705300

反応式

HRID 705300 の反応式
CS(O[C@@H:6]1[C@@H:11]([CH3:12])[CH2:10][C@@H:9]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[NH:19]C(OC(C)(C)C)=O)[CH2:8][C@H:7]1[NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])(=O)=O.[C-:35]#[N:36].[Na+].C(O)(C(F)(F)F)=O.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>CN(C=O)C.C(Cl)Cl.O1CCOCC1>[NH2:19][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:13]=1[C@H:9]1[CH2:8][C@@H:7]([NH:27][C:28](=[O:29])[O:30][C:31]([CH3:33])([CH3:34])[CH3:32])[C@@H:6]([C:35]#[N:36])[C@@H:11]([CH3:12])[CH2:10]1

参加物

8

反応物 4

HCID 6422Trifluoroacetic acidHCID 8929Sodium CyanideHCID 90495Di-tert-butyl dicarbonateHCID 86705223(1R,2R,4R,6S)-2-(tert-butoxycarbonylamino)-4-(3-(tert-butoxycarbonylamino)pyridin-4-yl)-6-methylcyclohexyl methanesulfonate

生成物 1

HCID 86705264(+/-)-tert-butyl (1R,2S,3S,5R)-5-(3-aminopyridin-4-yl)-2-cyano-3-methylcyclohexylcarbamate収率 20%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a solution of (+/−)-(1R,2R,4R,6S)-2-(tert-butoxycarbonylamino)-4-(3-(tert-butoxycarbonylamino)pyridin-4-yl)-6-methylcyclohexyl methanesulfonate (1.0 equiv.) in DMF (0.20 M) was added NaCN (5.0 equiv.). The solution was submerged in an 85° C. oil bath and left stirring under Ar for 16 hrs. The solution was cooled to rt and left stirring under Ar overnight. The solution was partitioned between EtOAc and H2O. The organic layer was washed with Na2CO3(sat), NaCl(sat), dried over MgSO4, filtered, concentrated. To a solution of the bis-Boc product (10 equiv.) in DCM (0.20 M) was added TFA (62.0 equiv.). The mixture was stirred at ambient temperature for 40 min and concentrated and neutralized with saturated aqueous sodium bicarbonate. Dioxane (0.15 M) and Boc2O (4.0 equiv.) were added. The reaction mixture was stirred vigorously at ambient temperature for 16 hrs. Volatiles were removed in vacuo. The aqueous phase was extracted with 10:1 DCM: MeOH. The combined extracts were dried over sodium sulfate, filtered, and concentrated. The crude material was purified by ISCO chromatography over silica gel to give (+/−)-tert-butyl (1R,2S,3S,5R)-5-(3-aminopyridin-4-yl)-2-cyano-3-methylcyclohexylcarbamate in 20% yield. LC/MS (m/z)=331.2 (MH+), Rt=0.62 min.

後処理

  1. customwas submerged in an 85° C.
  2. waitleft
  3. waitleft
  4. stirringstirring under Ar overnight
  5. customThe solution was partitioned between EtOAc and H2O
  6. washThe organic layer was washed with Na2CO3(sat), NaCl(sat)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. stirringThe mixture was stirred at ambient temperature for 40 min
  11. concentrationconcentrated and neutralized with saturated aqueous sodium bicarbonate
  12. stirringThe reaction mixture was stirred vigorously at ambient temperature for 16 hrs
  13. customVolatiles were removed in vacuo
  14. extractionThe aqueous phase was extracted with 10:1 DCM
  15. dry with materialThe combined extracts were dried over sodium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated
  18. customThe crude material was purified by ISCO chromatography over silica gel

出典と根拠

ORDレコード
ord-21b6a20e47124bb4ad50572251df190b
出典データセット
uspto-grants-2015_11
特許番号
US09173883B2

関連ノート

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