2,3-Dihydroxybutanedioic Acid → Erlotinib Hydrochloride

HRID 238997Notes

Reaction equation

HRID 238997 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.[NH2:22][C:23]1[CH:24]=[C:25]([C:29]#[CH:30])[CH:26]=[CH:27][CH:28]=1.C(O)(=O)C(C(C(O)=O)O)O>C(O)C>[CH3:16][O:15][CH2:14][CH2:13][O:12][C:9]1[CH:10]=[C:11]2[C:2]([NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]#[CH:30])[CH:24]=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

5

Reactant 3

HCID 8752,3-Dihydroxybutanedioic AcidHCID 104682Benzenamine, 3-ethynyl-HCID 112899424-Chloro-6,7-bis(2-methoxyethoxy)quinazoline

Product 1

HCID 176871Erlotinib Hydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
27.5 °C

Procedure

15.0 g of 4-chloro-6,7-bis(2-methoxyethoxy) quinazoline was suspended in 450 ml ethanol and 13.8 g of 3-aminophenyl acetylene was added at 25-30° C. Further 3.0 g tartaric acid was added. The reaction mass was stirred at 25-30° C. for 6 hours. Solid obtained was filtered, washed with water and dried under vacuum. This solid was suspended in water, basified with potassium hydroxide and stirred for 10 minutes. The resulting erlotinib base was isolated by filtration, washed with ethanol and dried under vacuum. The solid obtained was then suspended in water and acidified to pH 1.0-2.0 using hydrochloric acid. The reaction mixture was stirred for 2 hours, filtered, washed with water and dried at 40-45° C. to obtain 18.3 g of erlotinib hydrochloride.

Workup

  1. customSolid obtained
  2. filtrationwas filtered
  3. washwashed with water
  4. customdried under vacuum
  5. stirringstirred for 10 minutes

Sources & evidence

ORD record
ord-4cdbc0085e5e4bffada7bdf44fc86788
Source dataset
uspto-grants-2014_02
Patent number
US08642758B2

Reaction notes

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