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Diisopropylethylamine → ethyl (1S,2R,4R,6S)-2-amino-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexylcarbamate

HRID 879191
ノート
印刷プレビュー

反応式

HRID 879191 の反応式
[NH2:1][C@H:2]1[C@@H:7]([CH3:8])[CH2:6][C@@H:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[NH:15][C:16](=[O:32])[C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([C:24]3[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=3[F:31])[N:18]=2)[CH2:4][C@H:3]1[NH:33]C(=O)OC(C)(C)C.CCN([CH:47]([CH3:49])C)C(C)C.[C:50]([O-])([OH:52])=[O:51].[Na+]>C(Cl)Cl>[NH2:33][C@@H:3]1[CH2:4][C@H:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[NH:15][C:16](=[O:32])[C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([C:24]3[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=3[F:31])[N:18]=2)[CH2:6][C@H:7]([CH3:8])[C@@H:2]1[NH:1][C:50](=[O:51])[O:52][CH2:47][CH3:49]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 86705239tert-butyl (1R,2S,3S,5R)-2-amino-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-3-methylcyclohexylcarbamate

生成物 1

HCID 72548918ethyl (1S,2R,4R,6S)-2-amino-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexylcarbamate収率 14%

試薬・触媒・溶媒 1

HCID 6344
Dichloromethane
溶媒

実験手順

To a solution of tert-butyl (1R,2S,3S,5R)-2-amino-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-3-methylcyclohexylcarbamate (1.0 equiv.) in CH2Cl2 (0.03 M) at 0° C. was added DIEA (3.0 equiv.) and then ETHYL CHLOFORMATE (1.0 equiv.). The homogeneous solution was left standing at 0° C. at for 4 hrs. Neutralize the reaction with sat. NaHCO3 solution. The solution was partitioned between EtOAc and H2O. The organic layer was washed with Na2CO3(sat.), NaCl(sat.), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography. The Boc protected product was treated with 25% TFA/CH2Cl2 for 20 minutes at which time the volatiles were removed in vacuo and the residue was dissolved in DMSO and purified by RP-HPLC. The product fractions were lyophilized directly to yield ethyl (1S,2R,4R,6S)-2-amino-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexylcarbamate in 14% yield. LC/MS (m/z)=528.2 (MH+), Rt=0.65 min.

後処理

  1. waitThe homogeneous solution was left
  2. customstanding at 0° C. at for 4 hrs
  3. customThe solution was partitioned between EtOAc and H2O
  4. washThe organic layer was washed with Na2CO3(sat.), NaCl(sat.)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by ISCO SiO2 chromatography
  9. additionThe Boc protected product was treated with 25% TFA/CH2Cl2 for 20 minutes at which time the volatiles
  10. customwere removed in vacuo
  11. dissolutionthe residue was dissolved in DMSO
  12. custompurified by RP-HPLC

出典と根拠

ORDレコード
ord-58ac4a8fcf8b4dd89c28afae1883fe90
出典データセット
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08987457B2

反応ノート

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