Dimethylformamide → 2-{4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-yl}-2-methyl-propionitrile

HRID 1876208Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7]C(CNC2C3C(=CC=CC=3)N=C(CC#N)N=2)=[CH:5][CH:4]=1.Cl.ClCC1[N:36]=[C:35]([N:37]([C:39]2[CH:44]=[CH:43][C:42](OC)=[CH:41][CH:40]=2)C)[C:34]2[C:29](=CC=C[CH:33]=2)[N:28]=1.[C:47]([O-])([O-])=O.[Na+].[Na+].[C-]#N.[Na+].[CH3:56][N:57]([CH:59]=O)[CH3:58]>CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:59]([N:57]([CH3:56])[C:58]2[C:40]3[C:39](=[CH:44][CH:43]=[CH:42][CH:41]=3)[N:37]=[C:35]([C:34]([CH3:33])([CH3:47])[C:29]#[N:28])[N:36]=2)=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

{4-[(4-Methoxyphenyl)methylamino]-quinazolin-2-yl}acetonitrile: A suspension of (2-chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine hydrochloride (985 mg, 2.8 mmol), Na2CO3 (465 mg, 4.4 mmol) and NaCN (151 mg, 3.1 mmol) in DMF (10 mL) was stirred at 70° C. overnight. The reaction was cooled to rt, diluted with EtOAc and washed with H2O. The organics were dried (MgSO4), filtered, concentrated and purified by gradient MPLC (SiO2, EtOAc/hexanes, 0-100%) to provide 310 mg (36%) of the title compound. 1H NMR (CDCl3) δ 7.75 (d, 1H), 7.57 (ddd, 1H), 7.17-7.11 (m, 2H), 7.06-6.91 (m, 4H), 4.05 (s, 2H), 3.86 (s, 3H), 3.63 (s, 3H); LC-MS (ESI+; 305 ([M+H]+)).

Workup

temperatureThe reaction was cooled to rt
washwashed with H2O
dry with materialThe organics were dried (MgSO4)
filtrationfiltered
concentrationconcentrated
custompurified by gradient MPLC (SiO2, EtOAc/hexanes, 0-100%)

Sources & evidence

ORD record: ord-4ab4549647c4437aa2ea116ff23414c1
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08309562B2

Reaction notes

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