Sodium hydride → 3-(7-Ethoxy-6-methoxyquinazolin-4-ylthio)aniline

HRID 631750Notes

Reaction equation

HRID 631750 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:5]=[C:6]([SH:10])[CH:7]=[CH:8][CH:9]=1.Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([O:24][CH2:25][CH3:26])=[C:19]([O:22][CH3:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C1COCC1>[CH2:25]([O:24][C:18]1[CH:17]=[C:16]2[C:21]([C:12]([S:10][C:6]3[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=3)[NH2:3])=[N:13][CH:14]=[N:15]2)=[CH:20][C:19]=1[O:22][CH3:23])[CH3:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 315773-AminothiophenolHCID 117705294-Chloro-7-ethoxy-6-methoxyquinazoline

Product 1

HCID 668768283-(7-Ethoxy-6-methoxyquinazolin-4-ylthio)anilineYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred slurry of sodium hydride (350 mg of a 60% dispersion in mineral oil, 8.80 mmol) in anhydrous THF (50 mL) at rt, was added 3-aminobenzenethiol (1.00 g, 9.17 mmol). After stirring for 30 mins, 4-chloro-7-ethoxy-6-methoxyquinazoline (prepared as described in Example 6A Steps 1 through 5) (1.91 g, 8.03 mmol) was added and the reaction mixture was stirred at rt for a further 4 h. The mixture was concentrated under reduced pressure and the resulting solid was washed with water (three times) then ethyl acetate (three times) to afford 3-(7-ethoxy-6-methoxyquinazolin-4-ylthio)aniline (2.36 g, 90%) as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.69 (s, 1H), 7.30-7.31 (m, 2H), 7.13 (m, 1H), 6.80 (s, 1H), 6.72-6.74 (m, 2H), 5.31 (brs, 2H), 4.25 (q, J=7 Hz, 2H), 3.97 (s, 3H), 1.43 (t, J=7 Hz, 3H); LC-MS (ESI) m/z 328 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at rt for a further 4 h
  2. concentrationThe mixture was concentrated under reduced pressure
  3. washthe resulting solid was washed with water (three times)

Sources & evidence

ORD record
ord-42a3746816d9472190bff0b2a0891b57
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

Loading…