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

HRID 1467399Notes

Reaction equation

HRID 1467399 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-46d08ce57f1347f096a391d6a53d97aa
Source dataset
uspto-grants-2015_04
Patent number
US09000162B2

Reaction notes

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