Formic Acid → (S)-4-Amino-N-(1-cyano-2-(4-(2-methyl-1-oxoisoindolin-5-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamide

HRID 216979ノート

反応式

HRID 216979 の反応式
[C:1]([C@@H:3]([NH:22][C:23]([C:25]1([NH:31]C(=O)OC(C)(C)C)[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)=[O:24])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[C:16](=[O:20])[N:15]([CH3:21])[CH2:14]3)=[CH:7][CH:6]=1)#[N:2].C(O)=O.C(#N)C>CO.O>[NH2:31][C:25]1([C:23]([NH:22][C@H:3]([C:1]#[N:2])[CH2:4][C:5]2[CH:6]=[CH:7][C:8]([C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[C:16](=[O:20])[N:15]([CH3:21])[CH2:14]4)=[CH:9][CH:10]=2)=[O:24])[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1

参加物

6

反応物 3

HCID 284Formic AcidHCID 6342AcetonitrileHCID 59568607(S)-tert-Butyl 4-(1-cyano-2-(4-(2-methyl-1-oxoisoindolin-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

生成物 1

HCID 49783986(S)-4-Amino-N-(1-cyano-2-(4-(2-methyl-1-oxoisoindolin-5-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamide収率 60.3%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 962Water溶媒

反応条件

温度
50 °C

実験手順

To (S)-tert-butyl 4-(1-cyano-2-(4-(2-methyl-1-oxoisoindolin-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 31, step (v), 436 mg) was added formic acid (9.7 mL) and the mixture heated to 50° C. for 15 min. The mixture was allowed to cool to room temperature, diluted with methanol and then evaporated to dryness. The material was purified by reversed phase HPLC (Waters X-Bridge column) eluting with methanol in aqueous 0.1% trifluoroacetic acid as eluent. The fractions containing the desired compound were combined, evaporated and then dissolved in dichloromethane and washed with saturated aqueous sodium hydrogen carbonate. The organic layer was dried over magnesium sulfate and evaporated. The residue was triturated with diethyl ether and evaporated to give a product that was slurried in water (6.9 mL) and acetonitrile (0.36 mL) for 4 days. The solid was collected by filtration, washed with water and then dried under vacuum at 50° C. to afford the titled compound (212 mg).

後処理

  1. temperatureto cool to room temperature
  2. customevaporated to dryness
  3. customThe material was purified by reversed phase HPLC (Waters X-Bridge column)
  4. washeluting with methanol in aqueous 0.1% trifluoroacetic acid as eluent
  5. additionThe fractions containing the desired compound
  6. customevaporated
  7. dissolutiondissolved in dichloromethane
  8. washwashed with saturated aqueous sodium hydrogen carbonate
  9. dry with materialThe organic layer was dried over magnesium sulfate
  10. customevaporated
  11. customThe residue was triturated with diethyl ether
  12. customevaporated
  13. customto give a product that
  14. filtrationThe solid was collected by filtration
  15. washwashed with water
  16. customdried under vacuum at 50° C.

出典と根拠

ORDレコード
ord-2a23cfddd47d4628b229a8e9ec7e5bea
出典データセット
uspto-grants-2012_06
特許番号
US08193239B2

反応ノート

読み込み中…