Trifluoroacetic acid → N-((3S,4R)-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)pyrrolidin-3-yl)acrylamide

HRID 56384Notes

Reaction equation

HRID 56384 reaction equation
[C:1]([NH:5][C@@H:6]1[C@H:10]([NH:11][C:12]2[N:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:22]4[C:27]([Cl:28])=[C:26]([O:29][CH3:30])[CH:25]=[C:24]([O:31][CH3:32])[C:23]=4[Cl:33])[CH:18]=3)[N:13]=2)[CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7]1)(=[O:4])[CH:2]=[CH2:3].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:28][C:27]1[C:26]([O:29][CH3:30])=[CH:25][C:24]([O:31][CH3:32])=[C:23]([Cl:33])[C:22]=1[C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([NH:11][C@@H:10]1[CH2:9][NH:8][CH2:7][C@@H:6]1[NH:5][C:1](=[O:4])[CH:2]=[CH2:3])[N:21]=[CH:20]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131736918HCID 131736918, compound

Product 1

HCID 118036553N-((3S,4R)-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)pyrrolidin-3-yl)acrylamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl (3S,4R)-3-acrylamido-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)pyrrolidine-1-carboxylate (1.26 g, 2.14 mmol) in DCM (8 mL) and TFA (3 mL, 39 mmol) was stirred 3 h at room temperature. The excess solvents were removed under reduced pressure. The yellow oil was dissolved into DCM (˜100 mL) and washed with aqueous saturated sodium bicarbonate solution (˜50 mL). The aqueous layer was then extracted with fresh DCM (3×30 mL). The combined organic layers were dried over sodium sulfate, filtered, concentrated down, and dried to yield N-((3S,4R)-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)pyrrolidin-3-yl)acrylamide which was used without further purification in the next step.

Workup

  1. customThe excess solvents were removed under reduced pressure
  2. dissolutionThe yellow oil was dissolved into DCM (˜100 mL)
  3. washwashed with aqueous saturated sodium bicarbonate solution (˜50 mL)
  4. extractionThe aqueous layer was then extracted with fresh DCM (3×30 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated down
  8. customdried

Sources & evidence

ORD record
ord-276b3756a9ec4c418500b70ef8c5af56
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Reaction notes

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