Chloroform → Benzenamine, 3-ethynyl-

HRID 1184628Notes

Reaction equation

HRID 1184628 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:20]([NH:21][C:22]3[CH:23]=[CH:24][CH:25]=[C:26]([C:28]#[CH:29])[CH:27]=3)=[N:19][CH:18]=[N:17][C:9]2=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][O:15][CH3:16].Cl.CN(C)C=O.CN1CCCC1=O.C(Cl)(Cl)[Cl:44]>C(O)(C)C.N1C=CC=CC=1.O1CCOCC1.O1CCCC1.C(#N)C>[Cl:44][C:20]1[C:8]2[C:9](=[CH:10][C:11]([O:12][CH2:13][CH2:14][O:15][CH3:16])=[C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])[CH:7]=2)[N:17]=[CH:18][N:19]=1.[C:28]([C:26]1[CH:27]=[C:22]([CH:23]=[CH:24][CH:25]=1)[NH2:21])#[CH:29]

Participants

11

Reactant 4

HCID 6212ChloroformHCID 6228DimethylformamideHCID 13387N-methyl-2-pyrrolidoneHCID 176871Erlotinib Hydrochloride

Product 2

HCID 104682Benzenamine, 3-ethynyl-HCID 112899424-Chloro-6,7-bis(2-methoxyethoxy)quinazoline

Reagents, catalysts & solvents 5

HCID 1049PyridineSolventHCID 3776IsopropanolSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

The U.S. Pat. No. 5,747,498 (herein after referred to as the '498 patent) makes no reference to the existence of specific polymorphic forms of erlotinib hydrochloride. In this patent, it is disclosed that the compound is isolated according to conventional techniques; more precisely, according to the embodiments exemplified, crude erlotinib hydrochloride residue (obtained by reaction of 4-chloro-6,7-bis-(2-methoxyethoxy)-quinazoline with 3-ethynylaniline or its hydrochloride salt in a solvent such as a C1-C6-alcohol, dimethylformamide, N-methylpyrrolidin-2-one, chloroform, acetonitrile, tetrahydrofuran, 1,4-dioxane, pyridine or other aprotic solvents, preferably isopropanol) is basified with saturated aqueous NaHCO3 in the presence of methanol and chloroform followed by flash chromatography on silica using 30% acetone in hexane to afford erlotinib free base, which is further treated with hydrochloric acid in the presence of diethyl ether and chloroform to give erlotinib hydrochloride (melting point: 228°-230° C.).

Workup

  1. customis isolated

Sources & evidence

ORD record
ord-4cc912067d0d4a8a9a4bf5973402b94b
Source dataset
uspto-grants-2014_03
Patent number
US08669265B2

Reaction notes

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