Tetrahydrofuran → Afatinib dimaleate

HRID 1471802Notes

Reaction equation

HRID 1471802 reaction equation
[CH3:1][N:2]([CH2:4]/[CH:5]=[CH:6]/[C:7]([NH:9][C:10]1[CH:11]=[C:12]2[C:25]([NH:26][C:27]3[CH:28]=[CH:29][C:30]([F:34])=[C:31]([Cl:33])[CH:32]=3)=[N:24][CH:23]=[N:22][C:13]2=[CH:14][C:15]=1[O:16][C@@H:17]1[CH2:21][O:20][CH2:19][CH2:18]1)=[O:8])[CH3:3].[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]\[C:38]([OH:40])=[O:39].C1COCC1>>[CH3:3][N:2]([CH3:1])[CH2:4]/[CH:5]=[CH:6]/[C:7]([NH:9][C:10]1[CH:11]=[C:12]2[C:13]([N:22]=[CH:23][N:24]=[C:25]2[NH:26][C:27]2[CH:28]=[CH:29][C:30]([F:34])=[C:31]([Cl:33])[CH:32]=2)=[CH:14][C:15]=1[O:16][C@H:17]1[CH2:18][CH2:19][O:20][CH2:21]1)=[O:8].[CH:36](/[C:35]([OH:42])=[O:41])=[CH:37]/[C:38]([OH:40])=[O:39].[CH:36](/[C:35]([OH:42])=[O:41])=[CH:37]/[C:38]([OH:40])=[O:39]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran3×HCID 444266Maleic AcidHCID 10184653Afatinib

Product 1

HCID 15606394Afatinib dimaleateYield 85.3%

Procedure

THF (0.5 ml) was added to 200 mg (0.41 mmol) afatinib free base and the mixture was stirred at room temperature to obtain a light yellow coloured solution. A solution of 100 mg (0.8 mmol) maleic acid in 0.5 ml THF was added over the course of 2 min. Another 4 ml THF were added and the mixture was stirred for 1 h. The solids were filtered off, rinsed with 2 ml THF and dried on a rotary evaporator at 48° C./3 mbar for 6 h to give 0.245 g (83% yield) of a white solid.

Workup

  1. customto obtain a light yellow coloured solution
  2. stirringthe mixture was stirred for 1 h
  3. filtrationThe solids were filtered off
  4. washrinsed with 2 ml THF
  5. customdried on a rotary evaporator at 48° C./3 mbar for 6 h

Sources & evidence

ORD record
ord-38a72fba135b4e9b9e60a21aee1c06f7
Source dataset
uspto-grants-2015_04
Patent number
US09012464B2

Reaction notes

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