2-(Methylsulfonyl)ethanamine → Lapatinib

HRID 1847206Notes

Reaction equation

HRID 1847206 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 185.9%

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. The reaction mixture was charged with 5% Pd—C (750 mg) and stirred under 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 solution was charged with dichloromethane (25 mL) followed by addition of the solution of p-toluenesulfonic acid monohydrate (4.4 g, 23.3 mmoL) in methanol (10 mL). The yellow solid which precipitated out was filtered after 2-8 hours and washed with 1:1 mixture of methanol and dichloromethane (20 mL). The solid obtained was dried under vacuum at 40-45° C. to provide Lapatinib (11.4 g, Yield=93%, HPLC purity>99%).

Workup

  1. stirringThe reaction mixture was stirred for 2-4 hours until reaction completion
  2. stirringstirred under 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 solution was charged with dichloromethane (25 mL)
  9. additionfollowed by addition of the solution of p-toluenesulfonic acid monohydrate (4.4 g, 23.3 mmoL) in methanol (10 mL)
  10. customThe yellow solid which precipitated out
  11. filtrationwas filtered after 2-8 hours
  12. washwashed with 1:1 mixture of methanol and dichloromethane (20 mL)
  13. customThe solid obtained
  14. customwas dried under vacuum at 40-45° C.

Sources & evidence

ORD record
ord-eb53290a236845758b2e30c650519dfd
Source dataset
uspto-grants-2015_02
Patent number
US08952154B2

Reaction notes

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