Methyl iodide → HCID 59242016, compound

HRID 1876214Notes

Reaction equation

HRID 1876214 reaction equation
Cl[CH2:2][C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH3:23])=[CH:17][C:16]=2[F:24])[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.Cl.ClCC1N=C(NC2C=CC(OCC)=CC=2F)C2C(=CC=CC=2)[N:29]=1.CI.[H-].[Na+]>C1COCC1>[NH2:29][CH2:2][C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH3:23])=[CH:17][C:16]=2[F:24])[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68516792(2-Chloromethyl-quinazolin-4-yl)-(4-ethoxy-2-fluoro-phenyl)-methyl-amineHCID 68519575(2-Chloromethyl-quinazolin-4-yl)-(4-ethoxy-2-fluoro-phenyl)-amine hydrochloride

Product 1

HCID 59242016HCID 59242016, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2-Chloromethyl-quinazolin-4-yl)-(4-ethoxy-2-fluoro-phenyl)-methyl-amine: To (2-chloromethyl-quinazolin-4-yl)-(4-ethoxy-2-fluoro-phenyl)-amine hydrochloride (531 mg, 1.5 mmol) dissolved in THF at 0° C. was added methyl iodide (1.89 mL, 30.3 mmol) and sodium hydride (363 mg, 15.1 mmol). The reaction was stirred at room temperature for 4 h then warmed to room temperature for 1 h. The reaction was quenched with H2O and diluted with EtOAc. The aqueous phase was extracted with EtOAc (3×10 mL). The combined organic phases were washed with brine, dried (MgSO4), concentrated and purified by gradient MPLC (0-100%, EtOAc/hexanes, SiO2) to give 341 mg of the title compound. 1H NMR (CDCl3) δ 7.83 (d, 1H), 7.59 (t, 1H), 7.31-7.04 (m, 3H), 6.75-6.69 (m, 2H), 4.74 (s, 2H), 4.02 (q, 2H), 3.58 (s, 3H), 1.45 (t, 3H); LC-MS (ESI+; 365 ([M+H]+)).

Workup

  1. temperaturethen warmed to room temperature for 1 h
  2. customThe reaction was quenched with H2O
  3. additiondiluted with EtOAc
  4. extractionThe aqueous phase was extracted with EtOAc (3×10 mL)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. custompurified by gradient MPLC (0-100%, EtOAc/hexanes, SiO2)

Sources & evidence

ORD record
ord-7b3e477c15ad4d13af0cf5b93063c600
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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