Sodium Acetate → HCID 59242040, compound

HRID 1876159Notes

Reaction equation

[C:1]([C:3]1[CH:10]=[CH:9][C:6]([NH:7][CH3:8])=[CH:5][CH:4]=1)#[N:2].Cl[C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]=[C:14]([CH3:22])[N:13]=1.CC([O-])=O.[Na+]>C1COCC1.O>[CH3:8][N:7]([C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]=[C:14]([CH3:22])[N:13]=1)[C:6]1[CH:9]=[CH:10][C:3]([C:1]#[N:2])=[CH:4][CH:5]=1

Participants

Conditions

Temperature: 23 °C

Procedure

To a solution of formic acid 30 mL and acetic anhydride 30 mL stirred at room temperature for 1 h was added a solution of 4-aminobenzonitrile 2.36 g (20.0 mmol) in CH2Cl2 150 mL dropwise at 0° C. The reaction mixture was stirred at room temperature for 4 h (EMI-mass: 146 [M]+). After concentration, the crude intermediate was dissolved in THF 50 mL, and was added BH3 in Me2S 15 mL. The reaction mixture was then stirred for 5 h under reflux. The crude product was extracted with EtOAc, washed with water, sat. Na2CO3 aqueous solution and dried on anhydrous MgSO4. After removal of solvents, 4-cyano-N-methylaniline was obtained in 80% purity based on GC/MS (EMI-mass: 132 [M]+). A mixture of crude 4-cyano-N-methylaniline 0.40 g (ca. 2 mmol) and 4-chloro-2-methylquinazoline 0.357 g (2.0 mmol) with NaOAc 0.2 g (2.3 mmol) in THF 20 mL and H2O 12 mL was stirred at 23° C. for 4 days. After removing solvents, the crude product was purified with preparative HPLC to give the titled compound in 1% yield (10 mg). 1H NMR (CD3OD, 400 MHz): δ 7.94 (d, 2H, J=8.8 Hz), 7.91-7.86 (m, 1H), 7.76-7.73 (m, 1H), 7.65 (d, 2H, J=8.8 Hz), 7.34-7.30 (m, 1H), 6.99-6.96 (m, 1H), 3.87 (s, 3H), 2.81 (s, 3H). m/e: 275.1420 (M+1).

Workup

customAfter removing solvents
customthe crude product was purified with preparative HPLC

Sources & evidence

ORD record: ord-13e0e26869d842e8ae660bb2f38ff38f
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08309562B2

Reaction notes

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