Ethylamine → HCID 67042034, compound

HRID 2400266Notes

Reaction equation

HRID 2400266 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[N:3]=1.[CH2:23]([NH2:25])[CH3:24]>C1COCC1>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([C:4]2[N:3]=[C:2]([CH2:24][CH2:23][NH2:25])[C:11]3[C:6](=[CH:7][C:8]([C:12]([F:15])([F:13])[F:14])=[CH:9][CH:10]=3)[N:5]=2)=[CH:17][CH:18]=1

Participants

4

Reactant 2

HCID 6341EthylamineHCID 86667782HCID 86667782, compound

Product 1

HCID 67042034HCID 67042034, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 4-chloro-2-(4-chloro-phenyl)-7-trifluoromethylquinazoline (52.0 g, 0.15 mol) in THF (400 mL) at 0° C. was added dropwise a solution of ethylamine (0.45 mol, 230 mL, 2 M in THF. The ice-bath was then removed and the reaction mixture was allowed to stir at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure then partitioned between ethyl acetate (400 mL) and water (400 mL) removing any undissolved solid by vacuum filtration. The filtrate was concentrated to approximately 200 mL and the resultant precipitate was removed by vacuum filtration. The filtrate was again concentrated to approximately 100 mL volume and the resultant precipitate was removed by vacuum filtration. Finally the filtrate was cooled to 0° C. upon which [2-(4-chloro-phenyl)-7-trifluoromethyl-quinazolin-4-yl]ethylamine precipitated from solution. The precipitate (30 g) was isolated by vacuum filtration and dried under vacuum (10 mbar, 50° C.). A second amount of the precipitate of equal purity (19.6 g) was obtained following concentration of the filtrate to approximately 50 mL volume, cooling to 0° C., filtration and drying under vacuum. Combined yield=49.6 g, 93%; LC-MS: 2.9 min, 352 (M+); 1H NMR (DMSO-d6): δ 1.38 (t, 1 H, J=7 Hz), 3.77-3.85 (m, 2 H), 7.46 (d, 2 H, J=8.7 Hz), 7.64 (dd, 1 H, J=8.3, 1.8 Hz), 7.72-7.78 (br s, 1 H), 8.09 (s, 1 H), 8.17 (d, 1 H, J=8.3 Hz), 8.59 (d, 2 H, J=8.7 Hz).

Workup

  1. customThe ice-bath was then removed
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthen partitioned between ethyl acetate (400 mL) and water (400 mL)
  4. customremoving any undissolved solid
  5. filtrationby vacuum filtration
  6. concentrationThe filtrate was concentrated to approximately 200 mL
  7. customthe resultant precipitate was removed by vacuum filtration
  8. concentrationThe filtrate was again concentrated to approximately 100 mL volume
  9. customthe resultant precipitate was removed by vacuum filtration
  10. temperatureFinally the filtrate was cooled to 0° C. upon which [2-(4-chloro-phenyl)-7-trifluoromethyl-quinazolin-4-yl]ethylamine
  11. customprecipitated from solution

Sources & evidence

ORD record
ord-29c64feb0faa4a45a1c6330dbdb39ba7
Source dataset
uspto-grants-2014_08
Patent number
US08796180B2

Reaction notes

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