Trifluoroacetic acid → N-Dealkylated lapatinib

HRID 415009Notes

Reaction equation

HRID 415009 reaction equation
C(OC(=O)[NH:7][CH2:8][C:9]1[O:10][C:11]([C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[N:20]=[CH:19][N:18]=[C:17]3[NH:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=3)=[C:27]([Cl:40])[CH:26]=2)=[CH:12][CH:13]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][CH2:8][C:9]1[O:10][C:11]([C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[N:20]=[CH:19][N:18]=[C:17]3[NH:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=3)=[C:27]([Cl:40])[CH:26]=2)=[CH:12][CH:13]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66623782(5-(4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-yl)-furan-2-ylmethyl)-carbamic acid tert-butyl ester

Product 1

HCID 21952026N-Dealkylated lapatinibYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(5-(4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-yl)-furan-2-ylmethyl)-carbamic acid tert-butyl ester (0.0218 g, 0.0379 mmol) is dissolved in DCM (2 ml) and TFA (2 ml) is added dropwise. The reaction mixture is stirred at room temperature for 1 hour. The solvent is removed under a nitrogen stream and to the residue are added consecutively saturated aqueous potassium carbonate solution and DCM. The resulting mixture is extracted with DCM containing 5% THF, the combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure to yield 17.6 mg (0.037 mmol, 98%) of the clean desired product.

Workup

  1. customThe solvent is removed under a nitrogen stream
  2. additionto the residue are added consecutively saturated aqueous potassium carbonate solution and DCM
  3. extractionThe resulting mixture is extracted with DCM containing 5% THF
  4. dry with materialthe combined organic extracts are dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5ea2c5075c8b4d43983c1c966ca4020f
Source dataset
uspto-grants-2012_01
Patent number
US08088766B2

Reaction notes

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