Sodium Cyanide → 4-[(4-Methoxyphenyl)(methyl)amino]quinazoline-2-carbonitrile

HRID 1876152Notes

Reaction equation

HRID 1876152 reaction equation
Cl.Cl[C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.[C-]#N.[Na+].[N:26]12CCN(CC1)C[CH2:27]2>CS(C)=O.CC(O)C.O.C(OCC)(=O)C>[CH3:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([N:13]([CH3:14])[C:11]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]=[C:3]([C:27]#[N:26])[N:12]=2)=[CH:16][CH:17]=1

Participants

8

Reactant 3

HCID 8929Sodium CyanideHCID 9237DabcoHCID 86639964(2-Chloroquinazolin-4-yl)-(4-methoxyphenyl)-methylamine hydrochloride

Product 1

HCID 575165474-[(4-Methoxyphenyl)(methyl)amino]quinazoline-2-carbonitrileYield 139.4%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of (2-chloroquinazolin-4-yl)-(4-methoxyphenyl)-methylamine hydrochloride (56 mg, 0.17 mmol) in 1 mL of DMSO and 0.5 mL of 2-propanol were added sodium cyanide (16 mg, 0.34 mmol) and 1,4-diazabicyclo[2.2.2]octane (9 mg, 0.084 mmol). The mixture was heated at 35° C. for 1 d with stirring. The solution was diluted with 5 mL of water and 10 mL of ethyl acetate. The organic layer was washed with water, then dried and concentrated. The resulting crude material was purified by silica gel column chromatography to give the title compound (34 mg, 70%). 1H NMR (CDCl3, 400 MHz) δ 7.85 (d, 1H, J=8.4 Hz), 7.64 (t, 1H, J=6.8 Hz), 7.14 (m, 3H), 6.96 (m, 3H), 3.86 (s, 3H), 3.61 (s, 3H); ESI-MS m/z 291 (M+H)+.

Workup

  1. washThe organic layer was washed with water
  2. customdried
  3. concentrationconcentrated
  4. customThe resulting crude material was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-bfb59ba6a15e49e489559cf83a4456ce
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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