2-(Methylsulfonyl)ethanamine → Lapatinib

HRID 1847207Notes

Reaction equation

HRID 1847207 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([C:28]4[O:32][C:31]([CH:33]=O)=[CH:30][CH:29]=4)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.[NH2:35][CH2:36][CH2:37][S:38]([CH3:41])(=[O:40])=[O:39]>ClCCl.CO.[Pd]>[CH3:41][S:38]([CH2:37][CH2:36][NH:35][CH2:33][C:31]1[O:32][C:28]([C:25]2[CH:24]=[CH:23][C:22]3[N:21]=[CH:20][N:19]=[C:18]([NH:17][C:4]4[CH:5]=[CH:6][C:7]([O:8][CH2:9][C:10]5[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=5)=[C:2]([Cl:1])[CH:3]=4)[C:27]=3[CH:26]=2)=[CH:29][CH:30]=1)(=[O:40])=[O:39]

Participants

6

Reactant 2

HCID 43405612-(Methylsulfonyl)ethanamineHCID 11181296(5-(4-(4-((3-Fluorobenzyl)oxy)-3-chloroanilino)-6-quinazolinyl)-2-furancarboxaldehyde

Product 1

HCID 208908LapatinibYield 85%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

The suspension of 5-[4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl]-2-furaldehyde (5 g, 10.6 mmoL) in dichloromethane (50 mL) was charged with a solution of 2-aminoethylmethylsulfone (3.2 g, 11.7 mmoL) in methanol (25 mL) slowly under constant stirring at room temperature. The reaction mixture was stirred for 2-4 hours until reaction completion and then was charged with 5% Pd—C (750 mg) and stirred under a hydrogen atmosphere using balloon pressure for 12-16 hours until reaction completion. The obtained mixture was filtered through Celite® pad and rinsed with methanol (5 mL) and dichloromethane (15 mL) mixture. The filtrate was distilled to low volume and the obtained solution was charged with methanol (25 mL). The reaction mixture was stirred for 2-6 hours and the yellow solid which precipitated out was filtered and washed with methanol (10 mL). The solid obtained was dried under vacuum at 40-45° C. to furnish Lapatinib freebase (5 g, Yield=85%, HPLC purity>99%).

Workup

  1. stirringThe reaction mixture was stirred for 2-4 hours until reaction completion
  2. stirringstirred under a hydrogen atmosphere
  3. customfor 12-16 hours
  4. customuntil reaction completion
  5. filtrationThe obtained mixture was filtered through Celite® pad
  6. washrinsed with methanol (5 mL) and dichloromethane (15 mL) mixture
  7. distillationThe filtrate was distilled to low volume
  8. additionthe obtained solution was charged with methanol (25 mL)
  9. stirringThe reaction mixture was stirred for 2-6 hours
  10. customthe yellow solid which precipitated out
  11. filtrationwas filtered
  12. washwashed with methanol (10 mL)
  13. customThe solid obtained
  14. customwas dried under vacuum at 40-45° C.

Sources & evidence

ORD record
ord-34cbaaf313894d6e821842c20627607c
Source dataset
uspto-grants-2015_02
Patent number
US08952154B2

Reaction notes

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