Triethylamine → Benzyl 4-((5-bromo-2-pivalamidopyridin-4-ylamino)methyl)piperidine-1-carboxylate

HRID 556859Notes

Reaction equation

HRID 556859 reaction equation
[Br:1][C:2]1[C:3](Cl)=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[N:6][CH:7]=1.[NH2:16][CH2:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[CH2:20][CH2:19]1.C(N(CC)CC)C>CN1C(=O)CCC1>[Br:1][C:2]1[C:3]([NH:16][CH2:17][CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[O:25])[CH2:20][CH2:19]2)=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 219554994-Aminomethyl-1-N-Cbz-piperidineHCID 59613421N-(5-bromo-4-chloropyridin-2-yl)-2,2-dimethylpropanamide

Product 1

HCID 59613492Benzyl 4-((5-bromo-2-pivalamidopyridin-4-ylamino)methyl)piperidine-1-carboxylateYield 87.2%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
210 °C

Procedure

Two capped microwave reaction vials each containing a solution of N-(5-bromo-4-chloropyridin-2-yl)pivalamide (0.55 g, 1.89 mmol), benzyl 4-(aminomethyl)piperidine-1-carboxylate (1.07 g, 2 eq.) and triethylamine (0.80 mL, 3 eq.) in NMP (3.8 mL) were heated at 210° C. by microwave irradiation for 1.5 hr and then allowed to cool. The contents of the two vials were combined and partitioned between EtOAc (15 mL) and sat. NaHCO3 (150 mL). The organic layer was retained whilst the aqueous was further extracted with EtOAc (15 mL). The organic extracts were combined, washed with brine (50 mL), dried (MgSO4) and concentrated. The crude material was purified by chromatography on a 40+M Biotage silica column, eluting with a gradient of EtOAc in dichloromethane, to give the title compound as a clear oil (0.83 g, 43%)

Workup

  1. temperatureto cool
  2. custompartitioned between EtOAc (15 mL) and sat. NaHCO3 (150 mL)
  3. extractionaqueous was further extracted with EtOAc (15 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by chromatography on a 40+M Biotage silica column
  8. washeluting with a gradient of EtOAc in dichloromethane

Sources & evidence

ORD record
ord-90a6831844ba4adda8508b0b6e7e7f3c
Source dataset
uspto-grants-2011_11
Patent number
US08058045B2

Reaction notes

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