Dimethyl Sulfoxide → Erlotinib Hydrochloride

HRID 1942258Notes

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.CS(C)=O.[C:26]([C:28]1[CH:29]=[C:30]([CH:32]=[CH:33][CH:34]=1)[NH2:31])#[CH:27]>CO>[CH3:16][O:15][CH2:14][CH2:13][O:12][C:9]1[CH:10]=[C:11]2[C:2]([NH:31][C:30]3[CH:32]=[CH:33][CH:34]=[C:28]([C:26]#[CH:27])[CH:29]=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

Conditions

Temperature: 27.5 °C

Procedure

4-Chloro-6,7-bis-(2-methoxyethoxy)-quinazoline (50 gm) and dimethyl sulfoxide (250 ml) are added to methanol (500 ml) while stirred at 25-30° C., 3-ethynylaniline (20.5 gm) is added to the reaction mixture at 25-30° C. and then the contents are heated to 85° C. The reaction mass is stirred for 2 hours at 80-85° C., the mass is cooled to 25-30° C. and then stirred for 1 hour. The material is filtered, washed with a mixture of dimethyl sulfoxide (50 ml) and methanol (100 ml), and then dried at 60° C. under vacuum for 4 hours to give 60 gm of erlotinib hydrochloride [HPLC purity: 99.65%; Content of N-methoxyethyl impurity: 0.09% (at 1.14 RRT)].

Workup

temperaturethe contents are heated to 85° C
stirringThe reaction mass is stirred for 2 hours at 80-85° C.
temperaturethe mass is cooled to 25-30° C.
stirringstirred for 1 hour
filtrationThe material is filtered
washwashed with a mixture of dimethyl sulfoxide (50 ml) and methanol (100 ml)
customdried at 60° C. under vacuum for 4 hours

Sources & evidence

ORD record: ord-259701a42a4a4e1b89bb1c20aadff9f0
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08389531B2

Reaction notes

Loading…