Hydrochloric Acid → 3-Butyn-2-ol, 4-(3-aminophenyl)-2-methyl-

HRID 1942252Notes

Reaction equation

HRID 1942252 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.[ClH:24].[CH3:25][O:26][CH2:27][CH2:28][O:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][C:39]=1[O:40][CH2:41][CH2:42][O:43][CH3:44])[N:36]=[CH:35][N:34]=[C:33]2[NH:45][C:46]1[CH:47]=[C:48]([C:52]#[C:53][C:54]([CH3:57])([OH:56])[CH3:55])[CH:49]=[CH:50][CH:51]=1>CC(O)C.C(#N)C.C(Cl)(Cl)Cl.ClCCl.C1(C)C=CC=CC=1.C(COC)OC.C(OCC)C>[Cl:24][C:33]1[C:32]2[C:37](=[CH:38][C:39]([O:40][CH2:41][CH2:42][O:43][CH3:44])=[C:30]([O:29][CH2:28][CH2:27][O:26][CH3:25])[CH:31]=2)[N:36]=[CH:35][N:34]=1.[NH2:45][C:46]1[CH:47]=[C:48]([C:52]#[C:53][C:54]([CH3:57])([OH:56])[CH3:55])[CH:49]=[CH:50][CH:51]=1

Participants

13

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 9868438Erlotinib Impurity 14

Product 2

HCID 1122363-Butyn-2-ol, 4-(3-aminophenyl)-2-methyl-HCID 112899424-Chloro-6,7-bis(2-methoxyethoxy)quinazoline

Reagents, catalysts & solvents 7

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 3776IsopropanolSolventHCID 6212ChloroformSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

According to European Patent No. 1044969, erlotinib hydrochloride is prepared, either by (i) reacting 6,7-bis(2-methoxyethoxy)-N43-[(trimethylsilyl)ethynyl]phenyl-4-quinazolinamine monohydrochloride, obtained by the reaction of 4-chloro-6,7-bis(2-methoxyethoxy)quinazoline with a solution of 3-[(trimethylsilyl)ethynyl]aniline in 2-propanol at reflux, with tetra-n-butylammonium fluoride in an aprotic solvent such as tetrahydrofuran, diethyl ether, dimethoxyethane, toluene, dichloromethane and chloroform, and then treating the reaction mass with concentrated hydrochloric acid in 2-propanol; or (ii) reacting 4-[3-[[6,7-bis(2-methoxyethoxy)-4-quinazolinyl]amino]phenyl]-2-methyl-3-butyn-2-ol or its monohydrochloride salt, obtained by the reaction of 4-chloro-6,7-bis(2-methoxyethoxy)quinazoline with 4-(3-aminophenyl)-2-methyl-3-butyn-2-ol in acetonitrile at reflux, with an alkali-metal or alkaline-metal hydroxide such as sodium hydroxide, lithium hydroxide, cesium hydroxide, calcium hydroxide, magnesium hydroxide and potassium hydroxide, in an alcoholic solvent such as 1-butanol, 2-butanol and 2-propanol, and then treating the reaction mass with concentrated hydrochloric acid in an alcoholic solvent.

Sources & evidence

ORD record
ord-5554e15f645e49399214a428be8b22e5
Source dataset
uspto-grants-2013_03
Patent number
US08389531B2

Reaction notes

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