Sodium hydride → 3-(7-(2-Chloroethoxy)-6-methoxyquinazolin-4-ylthio)aniline

HRID 1918015Notes

Reaction equation

HRID 1918015 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([SH:8])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][Cl:27])=[C:19]([O:22][CH3:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1>C1COCC1>[Cl:27][CH2:26][CH2:25][O:24][C:18]1[CH:17]=[C:16]2[C:21]([C:12]([S:8][C:4]3[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=3)[NH2:1])=[N:13][CH:14]=[N:15]2)=[CH:20][C:19]=1[O:22][CH3:23]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 315773-AminothiophenolHCID 596829074-Chloro-7-(2-chloroethoxy)-6-methoxyquinazoline

Product 1

HCID 668763233-(7-(2-Chloroethoxy)-6-methoxyquinazolin-4-ylthio)aniline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In a round bottomed flask 3-aminothiophenol (279 mg, 2.23 mmol) was dissolved in 10 mL of dry THF. To this solution was added sodium hydride, 60% suspension in mineral oil, (86 mg, 2.23 mmol) and the reaction stirred for 30 minutes. 4-chloro-7-(2-chloro-ethoxy)-6-methoxy-quinazoline (610 mg, 2.23 mmol) from Example 35A was added as a 10 mL solution in THF, and the reaction stirred overnight at room temperature. The solution was then concentrated to dryness, and partitioned between ethyl acetate and water, and extracted with an additional portion of ethyl acetate. The extracts were combined, dried with magnesium sulfate, filtered, and concentrated to give 3-(7-(2-chloroethoxy)-6-methoxyquinazolin-4-ylthio)aniline as a yellow solid weighing 600 mg. 1H NMR (300 MHz, DMSO-d6) δ 8.70 (s, 1H), 7.47 (d, 2H), 7.17 (m, 1H), 6.83 (s, 1H), 6.72 (m, 2H), 4.51 (m, 2H), 4.05 (m, 3H), 3.89 (s, 3H), 3.51 (bs, 2H); LC-MS (ESI) m/z 362 (M+H)+.

Workup

  1. stirringthe reaction stirred overnight at room temperature
  2. concentrationThe solution was then concentrated to dryness
  3. custompartitioned between ethyl acetate and water
  4. extractionextracted with an additional portion of ethyl acetate
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1a0127687990471c9ca08e9972d10b38
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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