1H-1,2,4-Triazole → tert-butyl (1R,2S,3S,5R)-5-(3-aminopyridin-4-yl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)cyclohexylcarbamate

HRID 879181

反応式

HRID 879181 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.[NH:35]1[CH:39]=[N:38][CH:37]=[N:36]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[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]([CH3:32])([CH3:33])[CH3:34])[C@@H:6]([N:35]2[CH:39]=[N:38][CH:37]=[N:36]2)[C@@H:11]([CH3:12])[CH2:10]1.[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]([CH3:32])([CH3:33])[CH3:34])[C@H:6]([N:35]2[CH:39]=[N:38][CH:37]=[N:36]2)[C@H:11]([CH3:12])[CH2:10]1

参加物

6

反応物 3

HCID 92571H-1,2,4-TriazoleHCID 10796Cesium carbonateHCID 86705223(1R,2R,4R,6S)-2-(tert-butoxycarbonylamino)-4-(3-(tert-butoxycarbonylamino)pyridin-4-yl)-6-methylcyclohexyl methanesulfonate

生成物 2

HCID 86705225tert-butyl (1R,2S,3S,5R)-5-(3-aminopyridin-4-yl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)cyclohexylcarbamate収率 19%HCID 86705226tert-butyl (1S,2R,3R,5S)-5-(3-aminopyridin-4-yl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)cyclohexylcarbamate収率 19%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of (+/−)-(1R,2R,4R,6S)-2-(tert-butoxycarbonylamino)-4-(3-(tert-butoxycarbonylamino)pyridin-4-yl)-6-methylcyclohexyl methanesulfonate (1.0 equiv.), 1H-1,2,4-triazole (3.0 equiv.) and Cs2CO3 (3.0 equiv.) in DMF (0.15 M) was stirred at 80° C. for 5 hrs. The volatiles were removed in vacuo and the residue was partitioned between EtOAc and H2O. The organic layer was washed with Na2CO3(sat.), NaCl(sat.), dried over MgSO4, filtered, concentrated and purified by RP HPLC, followed by free basing by partitioning between an equal volume of EtOAc and Na2CO3, separating, washing with NaCl(sat.), drying over MgSO4, filtering, concentrating. Purification was completed via SFC (20% MeOH, 100 mL/min, AD column) to yield tert-butyl (1R,2S,3S,5R)-5-(3-aminopyridin-4-yl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)cyclohexylcarbamate (19% yield, 99% ee) and tert-butyl (1S,2R,3R,5S)-5-(3-aminopyridin-4-yl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)cyclohexylcarbamate (19% yield, 99% ee). LC/MS (m/z)=373.3 (MH+), Rt=0.54 min.

後処理

  1. customThe volatiles were removed in vacuo
  2. customthe residue was partitioned between EtOAc and H2O
  3. washThe organic layer was washed with Na2CO3(sat.), NaCl(sat.)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by RP HPLC
  8. customby partitioning between an equal volume of EtOAc and Na2CO3
  9. customseparating
  10. washwashing with NaCl(sat.)
  11. dry with materialdrying over MgSO4
  12. filtrationfiltering
  13. concentrationconcentrating
  14. customPurification

出典と根拠

ORDレコード
ord-50e7d7eefca641cbb84f14203f4f7812
出典データセット
uspto-grants-2015_03
特許番号
US08987457B2

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