Butyl vinyl ether → 8-(1-butoxyvinyl)-N-phenylquinazolin-2-amine

HRID 1056077Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[N:8]=[CH:7]2.C(=O)([O-])[O-].[K+].[K+].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:54]([O:56][CH2:57][CH2:58][CH2:59][CH3:60])=[CH2:55]>CN(C=O)C.O.C(O[Pd]OC(=O)C)(=O)C>[CH2:57]([O:56][C:54]([C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[N:8]=[CH:7]2)=[CH2:55])[CH2:58][CH2:59][CH3:60]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 8-bromo-N-phenylquinazolin-2-amine (310.3 mg, 1.034 mmol), diacetoxypalladium (23.21 mg, 0.103 mmol), potassium carbonate (286 mg, 2.068 mmol), 1,3-bis(diphenylphosphino)propane (94 mg, 0.227 mmol), and 1-(vinyloxy)butane (0.147 mL, 1.137 mmol) in a mixture of DMF (4.0 mL) and water (0.800 mL) was stirred under argon in a sealed tube at 70° C. for 3 d. The mixture was adsorbed onto silica gel (DMF was removed in vacuo). Chromatographic purification (silica gel, 0-50% EtOAc/hexanes, 20 min, 254 nm) furnished 8-(1-butoxyvinyl)-N-phenylquinazolin-2-amine (220 mg, 0.689 mmol, 67% yield) as a yellow solid: 1H NMR (400 MHz, CDCl3) δ ppm 9.06 (1H, s), 7.95 (1H, s), 7.90 (2H, d, J=8.2 Hz), 7.68 (1H, d, J=8.0 Hz), 7.34-7.37 (2H, m), 7.33 (1H, br. d, J=3.8 Hz), 7.31 (1H, d, J=7.8 Hz), 7.05 (1H, t, J=7.3 Hz), 4.99 (1H, d, J=1.0 Hz), 4.64 (1H, s), 3.99 (2H, t, J=6.7 Hz), 1.81 (2H, quin, J=7.1 Hz), 1.50 (2H, sxt, J=7.5 Hz), 0.96 (3H, t, J=7.4 Hz). m/z (ESI, +ve) 320.1 (M+H)+.

Workup

customChromatographic purification (silica gel, 0-50% EtOAc/hexanes, 20 min, 254 nm)

Sources & evidence

ORD record: ord-a529f403e3dc411ba92271698b64645f
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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