Stannane, tributyl(1-ethoxyethenyl)- → 2-(1-ethoxyvinyl)-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine

HRID 2036826Notes

Reaction equation

HRID 2036826 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.C([Sn](CCCC)(CCCC)[C:31]([O:33][CH2:34][CH3:35])=[CH2:32])CCC>O1CCOCC1>[CH2:34]([O:33][C:31]([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)=[CH2:32])[CH3:35]

Participants

4

Reactant 2

HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 866706132-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine

Product 1

HCID 670559512-(1-ethoxyvinyl)-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amineYield 85.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (1.0 g, 2.88 mmol) was added 1,4-dioxane (15 mL) and the resulting solution degassed with nitrogen. Pd(TPP)2Cl2 (0.202 g, 0.288 mmol) and tributyl(1-ethoxyvinyl)stannane (5.2 g, 14 mmol) were added under a nitrogen stream and the reaction mixture was heated to 90° C. where it stirred for 16 h. After this time, the reaction mixture was allowed to cool to room temperature. Once at the prescribed temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by neutral alumina column chromatography (20% ethyl acetate, hexane) to yield 2-(1-ethoxyvinyl)-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (940 mg, 85% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.23 (d, 1H, J=4.4 Hz), 7.75-7.85 (m, 2H), 7.70 (dt, 1H, J=2, 7.6 Hz), 7.45-7.58 (m, 5H), 7.20-7.30 (m, 3H), 6.61 (br s, 1H), 4.61 (s, 1H), 4.60 (d, 2H, J=4 Hz), 3.94 (q, 2H, J=6.8 Hz), 1.40 (t, 3H, J=6.8 Hz). LCMS Method Y: retention time 1.952 min, [M+1]=383.2.

Workup

  1. customthe resulting solution degassed with nitrogen
  2. temperatureto cool to room temperature
  3. concentrationOnce at the prescribed temperature, the reaction mixture was concentrated under reduced pressure
  4. customthe resulting residue was purified by neutral alumina column chromatography (20% ethyl acetate, hexane)

Sources & evidence

ORD record
ord-fc74f0c89ce7457ca2488eaab1c6a344
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

Loading…