Diisopropylethylamine → 4,6-bis-((3R,5S)-3,5-bis-(tert-Butoxycarbonylamino)-piperidin-1-yl)-3,5-dichloro-2-(4-acetylamino-phenyl-amino)-pyridine

HRID 1354828노트

반응식

HRID 1354828 반응식
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:14][C@H:13]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][N:11]([C:23]2[C:28]([Cl:29])=[C:27](F)[N:26]=[C:25]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([NH:38][C:39](=[O:41])[CH3:40])=[CH:34][CH:33]=3)[C:24]=2[Cl:42])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:43]([O:47][C:48]([NH:50][C@@H:51]1[CH2:56][C@H:55]([NH:57][C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH2:54][NH:53][CH2:52]1)=[O:49])([CH3:46])([CH3:45])[CH3:44].C(N(C(C)C)C(C)C)C>CN1C(=O)CCC1.CCOC(C)=O>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:14][C@H:13]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][N:11]([C:23]2[C:28]([Cl:29])=[C:27]([N:53]3[CH2:54][C@@H:55]([NH:57][C:58]([O:60][C:61]([CH3:63])([CH3:64])[CH3:62])=[O:59])[CH2:56][C@@H:51]([NH:50][C:48]([O:47][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:49])[CH2:52]3)[N:26]=[C:25]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([NH:38][C:39](=[O:41])[CH3:40])=[CH:34][CH:33]=3)[C:24]=2[Cl:42])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 21103719rac-tert-butyl N-[(3S,5R)-5-{[(tert-butoxy)carbonyl]amino}piperidin-3-yl]carbamateHCID 588654094-((3R,5S)-3,5-bis-(tert-butoxycarbonylamino)-piperidin-1-yl)-3,5-dichloro-2-(4-acetylamino-phenyl-amino)-6-fluoro-pyridine

생성물 1

HCID 588655374,6-bis-((3R,5S)-3,5-bis-(tert-Butoxycarbonylamino)-piperidin-1-yl)-3,5-dichloro-2-(4-acetylamino-phenyl-amino)-pyridine수율 43%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매

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온도
110 °C

실험 절차

4-((3R,5S)-3,5-bis-(tert-butoxycarbonylamino)-piperidin-1-yl)-3,5-dichloro-2-(4-acetylamino-phenyl-amino)-6-fluoro-pyridine (165) (0.29 g, 0.463 mmol) and cis-3,5-bis-(tert-butoxycarbonylamino)-piperidine (4) (0.219 g, 0.695 mmol) were combined and suspended in NMP (3.5 mL) in a 40 mL I-Chem vial. iPr2EtN (0.926 mmol) was added and the mixture was sonicated for 2 minutes. The mixture was heated to 110° C. and within 30 minutes all of the solids had dissolved. The solution continued to shake in the Teflon septum capped vial for 5 days. LC-MS indicated nearly complete reaction at this point. The solution was diluted with EtOAc (100 mL), washed with H2O (50 mL) and brine (50 mL), dried over MgSO4 and concentrated to give a brown oil which eventually solidified. Trituration of the solid with EtOAc followed by collection via filtration under reduced pressure gave the desired product (166) as a beige powder (0.183 g, 0.198 mmol, 43% yield). LC-MS (ESI): (exact mass: 921.43) m/e=922.6 [M+1]+.

후처리

  1. customthe mixture was sonicated for 2 minutes
  2. dissolutionhad dissolved
  3. customcapped vial for 5 days
  4. customreaction at this point
  5. washwashed with H2O (50 mL) and brine (50 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customto give a brown oil which
  9. filtrationTrituration of the solid with EtOAc followed by collection via filtration under reduced pressure

출처 및 근거

ORD 기록
ord-0f45991ff0ae462c9d433e81dc88f888
출처 데이터셋
uspto-grants-2007_05
특허 번호
US07223759B2

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