Sodium hydride → 3-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-ylthio)aniline

HRID 871594Notes

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][CH2:26][O:27][CH3:28])=[C:19]([O:22][CH3:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>O1CCCC1>[CH3:23][O:22][C:19]1[CH:20]=[C:21]2[C:16](=[CH:17][C:18]=1[O:24][CH2:25][CH2:26][O:27][CH3:28])[N:15]=[CH:14][N:13]=[C:12]2[S:10][C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=1)[NH2:3]

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of sodium hydride (422 mg, 17.6 mmol) in anhydrous tetrahydrofuran (100 mL) cooled to 0° C., 3-aminothiophenol (125 mg, 16.8 mmol) was added dropwise as a solution in tetrahydrofuran (5 mL). The mixture was stirred at 0° C. for 30 minutes. 4-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline, previously synthesized, was added and the resulting mixture heated to 50° C. overnight. After removal of the solvent the residue was taken into ethyl acetate/water, the organic layer separated and the aqueous phase extracted twice. The organics were combined, dried (MgSO4) and concentrated under reduced pressure. The residue was triturated in methanol to give 3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-ylthio)aniline (2.8 g, 49%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 8.69 (s, 1H), 7.33 (d, 2H), 7.16-7.10 (m, 1H), 6.81 (s, 1H), 6.75-6.67 (m, 2H), 5.35 (bs, 2H), 4.33 (bs, 2H), 4.02 (s, 6H), 3.77 (bs, 2H); LC-MS (ESI) m/z 358 (M+H)+.

Workup

additionwas added
temperaturethe resulting mixture heated to 50° C. overnight
customAfter removal of the solvent the residue
customthe organic layer separated
extractionthe aqueous phase extracted twice
dry with materialdried (MgSO4)
concentrationconcentrated under reduced pressure
customThe residue was triturated in methanol

Sources & evidence

ORD record: ord-afb533d506fc422984f62200db80d7df
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969587B2

Reaction notes

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