Diisopropylethylamine → HCID 90220161、化合物

HRID 2199781ノート

反応式

HRID 2199781 の反応式
FC1C(O[C:9](=[O:31])[NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]3[S:18][C:19]([NH:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=4)=[C:20]([C:22]#[N:23])[N:21]=3)[CH2:12]2)=C(F)C(F)=C(F)C=1F.[CH2:36]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38][NH:37]1.C(N(C(C)C)CC)(C)C>O1CCCC1>[C:22]([C:20]1[N:21]=[C:17]([N:13]2[CH2:14][CH2:15][CH2:16][C@@H:11]([NH:10][C:9]([N:37]3[CH2:38][C:39]4[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=4)[CH2:36]3)=[O:31])[CH2:12]2)[S:18][C:19]=1[NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1)#[N:23]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 422478IsoindolineHCID 118556246HCID 118556246、化合物

生成物 1

HCID 90220161HCID 90220161、化合物収率 50.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A solution of crude {(R)-1-[4-cyano-5-(pyridin-2-ylamino)-thiazol-2-yl]-piperidin-3-yl}-carbamic acid pentafluorophenyl ester (˜50 μmol) in tetrahydrofuran (1 mL) was cooled to 0° C. under an atmosphere of argon and isoindoline (12.6 mg, 106 μmol) and diisopropylethylamine (20 μL, 115 μmol) were added. The reaction mixture was stirred at 0° C. for 1 hour then warmed to ambient temperature and stirred for an additional hour. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution (2 mL), poured into water (10 mL) and extracted with ethyl acetate (4×5 mL). The combined organic extracts were washed with brine (2×5 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by reverse phase chromatography using a 12 g C-18 column gradient eluted from 10% acetonitrile in water up to 100% acetonitrile. The product containing fractions were combined and concentrated in vacuo to a yellow solid. The yellow solid was taken up in dichloromethane, dried over sodium sulfate, filtered and concentrated in vacuo to give 1,3-dihydro-isoindole-2-carboxylic acid {(R)-1-[4-cyano-5-(pyridin-2-ylamino)-thiazol-2-yl]-piperidin-3-yl}-amide as a yellow viscous oil (11.3 mg, 50%).

後処理

  1. temperaturethen warmed to ambient temperature
  2. stirringstirred for an additional hour
  3. customThe reaction was quenched by the addition of saturated aqueous ammonium chloride solution (2 mL)
  4. additionpoured into water (10 mL)
  5. extractionextracted with ethyl acetate (4×5 mL)
  6. washThe combined organic extracts were washed with brine (2×5 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by reverse phase chromatography
  11. washeluted from 10% acetonitrile in water up to 100% acetonitrile
  12. additionThe product containing fractions
  13. concentrationconcentrated in vacuo to a yellow solid
  14. dry with materialdried over sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-20f0b056470147c7b9589768b8ed59ca
出典データセット
uspto-grants-2016_06
特許番号
US09359345B2

反応ノート

読み込み中…