Phosphorus oxychloride → 1-(4-chloro-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-2-yl)-N,N-dimethylmethanamine

HRID 241022Notes

Reaction equation

[CH3:1][N:2]([CH2:4][C:5]1[N:14]=[C:13](O)[C:12]2[CH2:11][C:10]([CH3:17])([CH3:16])[CH2:9][CH2:8][C:7]=2[N:6]=1)[CH3:3].O=P(Cl)(Cl)[Cl:20]>C(Cl)(Cl)Cl>[Cl:20][C:13]1[C:12]2[CH2:11][C:10]([CH3:17])([CH3:16])[CH2:9][CH2:8][C:7]=2[N:6]=[C:5]([CH2:4][N:2]([CH3:3])[CH3:1])[N:14]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of the final residue from step 2 in CHCl3 (10 mL) was added POCl3 (10 mL). The reaction mixture was heated (90° C.) for two hours and concentrated. This residue was partitioned between dichloromethane and aqueous sodium bicarbonate and the resulting organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by silica gel chromatography (5-10% concentrated aqueous ammonia in methanol) in chloroform provided 1-(4-chloro-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-2-yl)-N,N-dimethylmethanamine (1.3 g, 48% yield). 1H NMR (400 MHz, CD3OD) δ 4.52 (s, 2H), 3.02 (s, 6H), 2.98 (t, 2H), 2.61 (s, 2H), 1.71 (t, 2H), 1.06 (s, 6H); MS (ES) for C13H20ClN3: 254 (MH+)

Workup

concentrationconcentrated
customThis residue was partitioned between dichloromethane and aqueous sodium bicarbonate
washthe resulting organic layer was washed with brine
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by silica gel chromatography (5-10% concentrated aqueous ammonia in methanol) in chloroform

Sources & evidence

ORD record: ord-f4a5878109ad4752855e61476332faf7
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08648066B2

Reaction notes

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