Acetonitrile → (4-Chloro-phenyl)-{4-[(3S,4S)-4-hydroxy-1-(6-methoxy-2-trifluoromethyl-quinazolin-4-yl)-pyrrolidin-3-yl]-piperazin-1-yl}-methanone

HRID 241346ノート

反応式

HRID 241346 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH:16]3[CH:20]([OH:21])[CH2:19][NH:18][CH2:17]3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.C(#N)C.C1CCN2C(=NCCC2)CC1.Cl[C:37]1[C:46]2[C:41](=[CH:42][CH:43]=[C:44]([O:47][CH3:48])[CH:45]=2)[N:40]=[C:39]([C:49]([F:52])([F:51])[F:50])[N:38]=1>CO.CCOC(C)=O.CCOCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([C@@H:16]3[C@@H:20]([OH:21])[CH2:19][N:18]([C:37]4[C:46]5[C:41](=[CH:42][CH:43]=[C:44]([O:47][CH3:48])[CH:45]=5)[N:40]=[C:39]([C:49]([F:51])([F:52])[F:50])[N:38]=4)[CH2:17]3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1

参加物

8

反応物 4

HCID 6342AcetonitrileHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 341762774-Chloro-6-methoxy-2-(trifluoromethyl)quinazolineHCID 66968375(4-Chloro-phenyl)-[4-(4-hydroxy-pyrrolidin-3-yl)-piperazin-1-yl]-methanone

生成物 1

HCID 58450977(4-Chloro-phenyl)-{4-[(3S,4S)-4-hydroxy-1-(6-methoxy-2-trifluoromethyl-quinazolin-4-yl)-pyrrolidin-3-yl]-piperazin-1-yl}-methanone収率 80%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To 0.326 mmoles of (4-Chloro-phenyl)-[4-(4-hydroxy-pyrrolidin-3-yl)-piperazin-1-yl]-methanone (synthesis described above in Example 5), add 1.6 mL acetonitrile and 1.63 mmoles of DBU. The stirred solution was cooled in ice and then 0.358 mmoles of 4-chloro-6-methoxy-2-trifluoromethyl-quinazoline was added and the reaction mixture was allowed to stir for a period of 2.5 hours. For the workup, the reaction mixture was diluted with methanol and concentrated on the rotavap. To the concentrate about 35 mL of water was added and was extracted with 40 mL EtOAc. The organic layer was separated and washed with 35 mL of 1M aq K2CO3 soln, and brine, dried over MgSO4 and excess solvent was removed on rotavap to yield a crude oil. This was diluted with about 2 mL EtOAc and about 8 mL ether was added and the white solid obtained was filtered off and vacuum dried to give the title compound in 80% yield. LC-MS: m/z=536 (M++1)

後処理

  1. temperatureThe stirred solution was cooled in ice
  2. concentrationconcentrated on the rotavap
  3. additionTo the concentrate about 35 mL of water was added
  4. extractionwas extracted with 40 mL EtOAc
  5. customThe organic layer was separated
  6. washwashed with 35 mL of 1M aq K2CO3 soln
  7. dry with materialbrine, dried over MgSO4 and excess solvent
  8. customwas removed on rotavap
  9. customto yield a crude oil
  10. additionwas added
  11. customthe white solid obtained
  12. filtrationwas filtered off
  13. customvacuum dried

出典と根拠

ORDレコード
ord-46d9267f5a2648a68e3df86aa2bde3f6
出典データセット
uspto-grants-2014_02
特許番号
US08648197B2

反応ノート

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