Methyl iodide → 2-(Difluoro(5-fluoropyridin-2-yl)methyl)-7-methyl-4-(methylthio)quinazoline

HRID 473167Notes

Reaction equation

HRID 473167 reaction equation
[F:1][C:2]([F:22])([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=1)[C:3]1[N:12]=[C:11]([SH:13])[C:10]2[C:5](=[CH:6][C:7]([CH3:14])=[CH:8][CH:9]=2)[N:4]=1.[OH-].[Na+].I[CH3:26]>C(O)(C)C>[F:22][C:2]([F:1])([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=1)[C:3]1[N:12]=[C:11]([S:13][CH3:26])[C:10]2[C:5](=[CH:6][C:7]([CH3:14])=[CH:8][CH:9]=2)[N:4]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 178422991HCID 178422991, compound

Product 1

HCID 666103932-(Difluoro(5-fluoropyridin-2-yl)methyl)-7-methyl-4-(methylthio)quinazolineYield 60.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methylquinazoline-4-thiol (243 mg, ˜0.75 mmol) in isopropanol (5 mL) was added 1N NaOH (1.13 mL, 1.13 mmol), and the mixture was stirred at rt for 5 min. Iodomethane (0.06 mL, 0.90 mmol) was then added and the mixture was stirred at room temperature for 5 min. The mixture was concentrated under reduced pressure to afford a yellow solid that was collected and washed with water and methanol to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methyl-4-(methylthio)quinazoline as a light yellow solid (152 mg, 60%). (M+H)+. 1H NMR (300 MHz, DMSO-d6) δ 8.57-8.66 (m, 1H), 7.93-8.12 (m, 3H), 7.85 (s, 1H), 7.62-7.71 (m, 1H), 2.56 (s, 3H), 2.53 (s, 3H). LCMS (ESI) m/z 336 (M+H)+.

Workup

  1. stirringthe mixture was stirred at room temperature for 5 min
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customto afford a yellow solid
  4. customthat was collected
  5. washwashed with water and methanol

Sources & evidence

ORD record
ord-876e8a9c0fcd42fabab5a0808c403381
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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