Triethylamine → 4-(4,6,7-Trimethoxy-quinazolin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 2264448Notes

Reaction equation

HRID 2264448 reaction equation
Cl[C:2]1[N:11]=[C:10]([O:12][CH3:13])[C:9]2[C:4](=[CH:5][C:6]([O:16][CH3:17])=[C:7]([O:14][CH3:15])[CH:8]=2)[N:3]=1.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([NH2:31])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C(N(CC)CC)C>CN1C(=O)CCC1>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([NH:31][C:2]2[N:11]=[C:10]([O:12][CH3:13])[C:9]3[C:4](=[CH:5][C:6]([O:16][CH3:17])=[C:7]([O:14][CH3:15])[CH:8]=3)[N:3]=2)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 221203552-Chloro-4,6,7-trimethoxyquinazoline

Product 1

HCID 687835484-(4,6,7-Trimethoxy-quinazolin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl esterYield 15%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 2-chloro-4,6,7-trimethoxy-quinazoline (0.8 g, 3.14 mmol, 1.0 equiv) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (1.26 g, 6.28 mmol, 2.0 equiv; commercially available) in anhydrous NMP (8 mL) and triethylamine (2 mL) was heated by microwave irradiation to 170° C. for 1 h. 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 a gradient of toluene/ethyl acetate (4:1→2:1) providing 0.2 g (15%) of the title compound. MS (ISP): 419.4 [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 a gradient of toluene/ethyl acetate (4:1→2:1)

Sources & evidence

ORD record
ord-a560fd409a5549a48408e5d5a5ae2114
Source dataset
uspto-grants-2010_12
Patent number
US07855194B2

Reaction notes

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