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

HRID 1354828Notes

Reaction equation

HRID 1354828 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
110 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-0f45991ff0ae462c9d433e81dc88f888
Source dataset
uspto-grants-2007_05
Patent number
US07223759B2

Reaction notes

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