Trifluoroacetic acid → HCID 86664461, compound

HRID 2092906Notes

Reaction equation

HRID 2092906 reaction equation
[NH2:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][O:13][CH3:14])[C:7]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:6][C:3]=1[C:4]#[N:5].[C:20]([C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][CH:28]=1)[NH2:25])#[CH:21].[CH:29](OCC)(OCC)OCC.[F:39][C:40]([F:45])([F:44])[C:41]([OH:43])=[O:42]>C(O)C>[CH3:19][O:18][CH2:17][CH2:16][O:15][C:7]1[CH:6]=[C:3]2[C:4]([NH:25][C:24]3[CH:26]=[CH:27][CH:28]=[C:22]([C:20]#[CH:21])[CH:23]=3)=[N:5][CH:29]=[N:1][C:2]2=[CH:9][C:8]=1[O:10][CH2:11][CH2:12][O:13][CH3:14].[F:39][C:40]([F:45])([F:44])[C:41]([O-:43])=[O:42]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acid3×HCID 31214Ethyl orthoformateHCID 104682Benzenamine, 3-ethynyl-HCID 237255602-Amino-4,5-bis(2-methoxyethoxy)benzonitrile

Product 1

HCID 86664461HCID 86664461, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-Amino-4,5-bis(2-methoxyethoxy)benzonitrile (25 g) was charged into ethanol (350 ml) at 25° C. to 30° C. and stirred for 10 minutes to 15 minutes to get a clear solution. 3-ethynyl aniline (11.1 g) followed triethyl orthoformate (20.86 g) was charged into reaction mass at 25° C. to 30° C. Trifluoroacetic acid (3.8 ml) was added slowly drop-wise into the reaction mixture at 25° C. to 30° C. and stirred for 30 minutes at 25° C. to 30° C. Trifluoroacetic acid (3.8 ml) was added slowly drop wise to reaction mixture at 25° C. to 30° C. and stirred for 30 minutes at 25° C. to 30° C. Again, trifluoroacetic acid (3.8 ml) was added slowly drop wise to reaction mixture at 25° C. to 30° C. and stirred for 30 minutes at 25° C. to 30° C. The reaction mixture was refluxed for about 24 hours at 75° C. to 80° C. and Cooled to 25° C. to 30° C. Ethanol (˜150 ml) was recovered from the reaction mixture under vacuum at 55° C. to 60° C. The solution obtained was Cooled to 25° C. to 30° C. and stirred for about 18 hours at 25° C. to 30° C. The solid obtained was filtered, washed with ethanol (2×25 ml) and dried under vacuum for about 18 hours at 40° C. to 45° C. to give erlotinib trifluoroacetate.

Workup

  1. customto get a clear solution
  2. additionwas charged into reaction mass at 25° C. to 30° C
  3. stirringstirred for 30 minutes at 25° C. to 30° C
  4. customwise to reaction mixture at 25° C. to 30° C.
  5. stirringstirred for 30 minutes at 25° C. to 30° C
  6. customwise to reaction mixture at 25° C. to 30° C.
  7. stirringstirred for 30 minutes at 25° C. to 30° C
  8. temperatureThe reaction mixture was refluxed for about 24 hours at 75° C. to 80° C.
  9. temperatureCooled to 25° C. to 30° C
  10. customEthanol (˜150 ml) was recovered from the reaction mixture under vacuum at 55° C. to 60° C
  11. customThe solution obtained
  12. temperaturewas Cooled to 25° C. to 30° C.
  13. stirringstirred for about 18 hours at 25° C. to 30° C
  14. customThe solid obtained
  15. filtrationwas filtered
  16. washwashed with ethanol (2×25 ml)
  17. customdried under vacuum for about 18 hours at 40° C. to 45° C.

Sources & evidence

ORD record
ord-97ad8b6f6f4e41a2ae15ec5aa13854cc
Source dataset
uspto-grants-2013_05
Patent number
US08440823B2

Reaction notes

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