Ethanol → (5,8-Difluoroquinazolin-4-yl)-[2-(4-methoxy-3-methylphenyl)-ethyl]-amine

HRID 2386901Notes

Reaction equation

HRID 2386901 reaction equation
[C:1]([C:3]1[C:8]([F:9])=[CH:7][CH:6]=[C:5]([F:10])[C:4]=1[N:11]=[CH:12][N:13](C)C)#[N:2].Cl.[CH3:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=1[O:27][CH3:28])[CH2:21][CH2:22]N.C(O)C>C(O)(=O)C>[F:9][C:8]1[CH:7]=[CH:6][C:5]([F:10])=[C:4]2[C:3]=1[C:1]([NH:2][CH2:22][CH2:21][C:20]1[CH:24]=[CH:25][C:26]([O:27][CH3:28])=[C:18]([CH3:17])[CH:19]=1)=[N:13][CH:12]=[N:11]2

Participants

5

Reactant 3

HCID 702EthanolHCID 189756582-(4-Methoxy-3-methyl-phenyl)-ethylamine HydrochlorideHCID 59223042N'-(2-Cyano-3,6-difluorophenyl)-N,N-dimethylformamidine

Product 1

HCID 59222937(5,8-Difluoroquinazolin-4-yl)-[2-(4-methoxy-3-methylphenyl)-ethyl]-amineYield 58%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

N′-(2-Cyano-3,6-difluorophenyl)-N,N-dimethylformamidine (1.65 g, 7.9 mmol) and 3-methyl-4-methoxyphenethylamine hydrochloride (2.4 g, 11.8 mmol) were combined in acetic acid (2.55 mL) and absolute ethanol (15 mL) and heated to reflux for 16 h. Upon cooling, the solvent was removed under reduced pressure and the remaining solid was slurried with water, suction filtered and washed with water, dried in vacuum at 45° C. to give 1.51 g (58%) of (5,8-difluoroquinazolin-4-yl)-[2-(4-methoxy-3-methylphenyl)-ethyl]-amine as an off-white solid. LC/MS: 330.18 (M++1). 1H NMR (CDCl3): δ 8.67 (s, 1H), 7.35 (m, 1H), 6.94-7.09 (m, 3H), 6.79 (d, J=9.0 Hz, 1H), 6.65-6.80 (br, 1H), 3.87 (q, J=6.9 Hz, 2H), 3.83 (s, 3H), 2.93 (t, J=6.9 Hz, 2H), 2.22 (s, 3H). M.P. 162-169° C.

Workup

  1. temperatureto reflux for 16 h
  2. temperatureUpon cooling
  3. customthe solvent was removed under reduced pressure
  4. filtrationfiltered
  5. washwashed with water
  6. customdried in vacuum at 45° C.

Sources & evidence

ORD record
ord-87fe40096fb441609507aca9ddd0b78b
Source dataset
uspto-grants-2012_09
Patent number
US08268843B2

Reaction notes

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