Chloroacetonitrile → 2-(4-(Quinazolin-4-yl)piperazin-1-yl)acetonitrile

HRID 600472Notes

Reaction equation

HRID 600472 reaction equation
[N:1]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[CH:9][N:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:17][CH2:18][N:19](CC)CC.ClCC#N>C1COCC1>[N:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7]([N:1]2[CH2:6][CH2:5][N:4]([CH2:17][C:18]#[N:19])[CH2:3][CH2:2]2)=[N:8][CH:9]=1

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 8471TriethylamineHCID 18585334-Piperazin-1-ylquinazoline

Product 1

HCID 552058602-(4-(Quinazolin-4-yl)piperazin-1-yl)acetonitrileYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(piperazin-1-yl)quinazoline (1.8 g, 8.3 mmol) in THF (50 mL) was added NEt3 (20 mL, 150 mmol) and chloroacetonitrile (12 mL, 190 mmol) and the reaction was stirred 16 h. The reaction mixture was quenched with 50% saturated aqueous NaHCO3 and extracted with EtOAc (3×200 mL). The combined organics were purified by silica gel chromatography (50% EtOAc/hexanes to 80% EtOAc/hexanes) to yield 55 (1.6 g, 6.1 mmol, 73%) as an viscous yellow oil. 1H NMR: (500 MHz, CDCl3) δ 8.74 (s, 1H), 8.06 (d, J=8.6 Hz, 1H), 7.90 (d, J=8.5 Hz, 1H), 7.82-7.55 (m, 1H), 7.54-7.50 (m, 1H), 3.94-3.88 (m, 4H), 3.63 (s, 2H), 2.86-2.81 (m, 4H); LC/MS: (ES+) m/z (M+H)+=254; HPLC Rt=0.71 min., column O.

Workup

  1. customThe reaction mixture was quenched with 50% saturated aqueous NaHCO3
  2. extractionextracted with EtOAc (3×200 mL)
  3. customThe combined organics were purified by silica gel chromatography (50% EtOAc/hexanes to 80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-70497f208cad4104bc1f2bbf2ae09378
Source dataset
uspto-grants-2011_03
Patent number
US07902204B2

Reaction notes

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