Tri(butyl)vinyltin → 5-phenyl-N-(pyridin-2-ylmethyl)-2-vinylquinazolin-4-amine
Reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:3]=1.[CH2:26](C([Sn])=C(CCCC)CCCC)[CH2:27]CC>O1CCOCC1>[C:20]1([C:8]2[CH:7]=[CH:6][CH:5]=[C:4]3[C:9]=2[C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[N:11][C:2]([CH:26]=[CH2:27])=[N:3]3)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1Participants
Conditions
- Temperature
- 90 °C
Procedure
To a solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (0.5 g, 1.44 mmol) in 1,4-dioxane (10 mL) was added Pd(TPP)2Cl2 (0.101 g, 0.144 mmol) and tributylvinyltin (2.285 g, 7.20 mmol) under a nitrogen stream. Upon completion of addition, the reaction mixture was heated to reflux at 90° C. for 16 h. After this time, the reaction mixture was allowed to cool to room temperature and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (20% ethyl acetate, hexane) to yield 5-phenyl-N-(pyridin-2-ylmethyl)-2-vinylquinazolin-4-amine (0.38 g, 78% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.22 (dd, 1H, J=4.8 Hz), 7.76 (d, 1H, J=1.6 Hz), 7.75 (s, 1H), 7.70 (dt, 1H, J=2 Hz, 8 Hz), 7.45-7.56 (m, 5H), 7.20-7.28 (m, 3H), 6.72 (dd, 1H, J=10.4 Hz, 17.2 Hz), 6.64 (t, 1H, J=3.6 Hz), 6.56 (dd, 1H, J=1.6 Hz, 17.2 Hz), 5.67 (d, 1H, J=10.4 Hz), 4.62 (d, 2H, J=4.0 Hz). LCMS Method T: retention time 1.500 min; [M+1]=339.2; HPLC Method A2: purity 98.1%, retention time=8.74 min.
Workup
- additionUpon completion of addition
- temperaturethe reaction mixture was heated
- temperatureto cool to room temperature
- concentrationconcentrated under reduced pressure
- customThe resulting residue was purified by silica gel column chromatography (20% ethyl acetate, hexane)
Sources & evidence
- ORD record
- ord-07d4892214ca43d6a6b98b9a6e23ee98
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08575184B2
Reaction notes
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