rac-tert-butyl N-[(3S,5R)-5-{[(tert-butoxy)carbonyl]amino}piperidin-3-yl]carbamate → N-[2-Benzyloxy-4-(4,6-bis-((3R,5S)-3,5-bis-(tert-Butoxycarbonylamino)-piperidin-1-yl)-[1,3,5]triazin-2-ylamino)-phenyl]-acetamide

HRID 1354857Notes

Reaction equation

HRID 1354857 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][NH:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:23]([O:30][C:31]1[CH:36]=[C:35]([NH:37][C:38]2[N:43]=[C:42](Cl)[N:41]=[C:40](Cl)[N:39]=2)[CH:34]=[CH:33][C:32]=1[NH:46][C:47](=[O:49])[CH3:48])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN(C=O)C>[CH2:23]([O:30][C:31]1[CH:36]=[C:35]([NH:37][C:38]2[N:43]=[C:42]([N:11]3[CH2:12][C@@H:13]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:10]3)[N:41]=[C:40]([N:11]3[CH2:12][C@@H:13]([NH:15][C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])[CH2:14][C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:10]3)[N:39]=2)[CH:34]=[CH:33][C:32]=1[NH:46][C:47](=[O:49])[CH3:48])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

4

Reactant 2

HCID 21103719rac-tert-butyl N-[(3S,5R)-5-{[(tert-butoxy)carbonyl]amino}piperidin-3-yl]carbamateHCID 21103875N-[2-Benzyloxy-4-(4,6-dichloro-[1,3,5]triazin-2-ylamino)-phenyl]-acetamide

Product 1

HCID 58865836N-[2-Benzyloxy-4-(4,6-bis-((3R,5S)-3,5-bis-(tert-Butoxycarbonylamino)-piperidin-1-yl)-[1,3,5]triazin-2-ylamino)-phenyl]-acetamideYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

(3R,5S)-3,5-bis-(tert-Butoxycarbonylamino)-piperidine (4) (1.68 g, 5.33 mmol) was suspended in DMF (20 mL), sonicated for 2 minutes and added to the crude reaction mixture containing N-[2-benzyloxy-4-(4,6-dichloro-[1,3,5]triazin-2-ylamino)-phenyl]-acetamide (400). The mixture was heated to 80° C. for 8 h. LC-MS indicated complete reaction at this point. The mixture was concentrated to a volume of 50 mL and poured into ice-water. A white solid precipitated immediately and was collected by filtration under reduced pressure followed by drying under high vacuum for 16 h to give the desired product (401) as a white powder (2.32 g, 2.4 mmol, 95% total yield for two steps). LC-MS (ESI): (exact mass: 961.54) m/e=962.7 [M+1]+ (100%).

Workup

  1. customsonicated for 2 minutes
  2. additionadded to the crude
  3. customreaction mixture
  4. customreaction at this point
  5. concentrationThe mixture was concentrated to a volume of 50 mL
  6. additionpoured into ice-water
  7. customA white solid precipitated immediately
  8. filtrationwas collected by filtration under reduced pressure
  9. customby drying under high vacuum for 16 h

Sources & evidence

ORD record
ord-bc0f3492d4fe490b949849e61a3ed475
Source dataset
uspto-grants-2007_05
Patent number
US07223759B2

Reaction notes

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