Triethylamine → HCID 22031291, compound

HRID 1192288Notes

Reaction equation

HRID 1192288 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2Cl.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(N(CC)CC)C>CN1CCCC1=O.CCOC(C)=O>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([Br:1])[CH:3]=3)[N:8]=[CH:7][N:6]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 167703106-Bromo-4-chloro-quinazoline

Product 1

HCID 22031291HCID 22031291, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

A solution of the crude product from Step 1 (1.5 g), piperazine-1-carboxylic acid tert-butyl ester (2.29 g, 12.3 mmol) and triethylamine (2.15 mL, 15.4 mmol) in N-methylpyrrolidinone (50 mL) was stirred and heated at 80° C. for 2 hours. The solution was cooled to room temperature, diluted with EtOAc (200 mL), washed with water (3×200 mL) and dried over Na2SO4. The mixture was purified by silica gel column chromatography (50% EtOAc/hexanes) to give 4-(6-bromo-quinazolin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester as a colorless oil (1.5 g, 3.8 mmol, 85% from Step 1.) MS (APCI+) [M+H]+ 394.9 and 392.9. 1H NMR (CDCl3, 400 MHz) δ 8.76 (1H, s), 8.02 (1H, s), 7.84-7.78 (2H, m), 3.74 (4H, s), 3.66 (4H, s), 1.51 (9H, s.)

Workup

  1. temperatureThe solution was cooled to room temperature
  2. washwashed with water (3×200 mL)
  3. dry with materialdried over Na2SO4
  4. customThe mixture was purified by silica gel column chromatography (50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-2cd39677cc6e494cbbd4002ece281348
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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