4-Amino-1-Boc-piperidine → 4-[4-(2-Fluoro-phenyl)-quinazolin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2264452Notes

Reaction equation

HRID 2264452 reaction equation
Cl[C:2]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([NH2:32])[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20]>CN1C(=O)CCC1>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([NH:32][C:2]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[F:18])[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

4

Reactant 2

HCID 12682914-Amino-1-Boc-piperidineHCID 860461424-(2-Fluorophenyl)-2-Chloro-quinazoline

Product 1

HCID 687810194-[4-(2-Fluoro-phenyl)-quinazolin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl esterYield 66%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 2-chloro-4-(2-fluoro-phenyl)-quinazoline (0.8 g, 3.09 mmol, 1.0 equiv) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (0.81 g, 4.02 mmol, 1.3 equiv; commercially available) in anhydrous NMP (8 mL) was heated by microwave irradiation to 180° C. for 40 min. The organic phase was concentrated under reduced pressure and the residue extracted with dichloromethane (3×50 mL) from a sat. solution of sodium bicarbonate (100 mL). The combined organic phases were dried over MgSO4 and the product purified by column chromatography on silica eluting with heptane/ethyl acetate (10:1) providing 0.86 g (66%) of the title compound. MS (ISP): 423.3 [M+H]+.

Workup

  1. concentrationThe organic phase was concentrated under reduced pressure
  2. extractionthe residue extracted with dichloromethane (3×50 mL) from a sat. solution of sodium bicarbonate (100 mL)
  3. dry with materialThe combined organic phases were dried over MgSO4
  4. customthe product purified by column chromatography on silica eluting with heptane/ethyl acetate (10:1)

Sources & evidence

ORD record
ord-1391dbf864eb4e8fb6d49175c8c1e084
Source dataset
uspto-grants-2010_12
Patent number
US07855194B2

Reaction notes

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