Hydrochloric Acid → Erlotinib Hydrochloride

HRID 239001Notes

Reaction equation

HRID 239001 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[C:9]([O:12][CH2:13][CH2:14][O:15][CH3:16])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C1(C)C=CC=CC=1.[NH2:29][C:30]1[CH:31]=[C:32]([C:36]#[CH:37])[CH:33]=[CH:34][CH:35]=1.Cl>C(#N)C>[CH3:16][O:15][CH2:14][CH2:13][O:12][C:9]1[CH:10]=[C:11]2[C:2]([NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]#[CH:37])[CH:31]=3)=[N:3][CH:4]=[N:5][C:6]2=[CH:7][C:8]=1[O:17][CH2:18][CH2:19][O:20][CH3:21].[ClH:1]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 104682Benzenamine, 3-ethynyl-HCID 112899424-Chloro-6,7-bis(2-methoxyethoxy)quinazoline

Product 1

HCID 176871Erlotinib HydrochlorideYield 91.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
37.5 °C

Procedure

1.98 Kg of 4-chloro-6,7-bis (2-methoxyethoxy) quinazoline was suspended in 30 litres of acetonitrile and 10 litres of toluene and 1.0 Kg of 3-aminophenyl acetylene was charged at 25-30° C. and hydrochloric acid was added. The reaction mass was heated and stirred at 35-40° C. for 6 hours. The solid obtained was filtered and washed with a mixture of acetonitrile and toluene. The product was dried at 38-40° C. to obtain 2.5 Kg of erlotinib hydrochloride.

Workup

  1. temperatureThe reaction mass was heated
  2. customThe solid obtained
  3. filtrationwas filtered
  4. washwashed with a mixture of acetonitrile and toluene
  5. customThe product was dried at 38-40° C.

Sources & evidence

ORD record
ord-6027599214704f5aafedec897e1eb7d8
Source dataset
uspto-grants-2014_02
Patent number
US08642758B2

Reaction notes

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