Diisopropylethylamine → HCID 67539976, compound

HRID 1192433Notes

Reaction equation

HRID 1192433 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.CCN(C(C)C)C(C)C.[C:24]([N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]>CC(O)C>[N+:12]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][N:3]=[C:2]2[N:34]1[CH2:33][CH2:32][N:31]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:36][CH2:35]1)([O-:14])=[O:13]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 113562574-Chloro-6-nitroquinazoline

Product 1

HCID 67539976HCID 67539976, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 4-chloro-6-nitroquinazoline (prepared according to the literature: Alexander J. Bridges et al. J. Med. Chem. 1996, 39, 267-276, and references therein; 12 g, 57.5 mmol) and DIEA (10 mL, 57.5 mmol) in 230 mL IPA was added Boc-piperazine (10.7 g, 57.5 mmol). The reaction mixture was heated to 60° C. and stirred for 13 hours, after which it was cooled to room temperature and concentrated by rotary evaporation. The residue was dissolved in dichloromethane (DCM) and washed with 1N NaOH. The organic layer was dried (Na2SO4), filtered, and concentrated by rotary evaporation. The resulting oil was purified on silica gel (1:1 to 1:4 DCM:EtOAc gradient) to furnish 4-(6-nitro-quinazolin-4-yl)-1-Boc-piperazine as a pale yellow oil (18.3 g, 89%). LCMS (APCI+) m/z 360 [M+H]+. HPLC Rt 3.06 min.

Workup

  1. temperatureafter which it was cooled to room temperature
  2. concentrationconcentrated by rotary evaporation
  3. dissolutionThe residue was dissolved in dichloromethane (DCM)
  4. washwashed with 1N NaOH
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation
  8. customThe resulting oil was purified on silica gel (1:1 to 1:4 DCM:EtOAc gradient)

Sources & evidence

ORD record
ord-e76225abe0414930b0f6920b8d5ed5fd
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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