Sulfoximine, S,S-dimethyl- → N-(2-benzyloxy-4-fluoro-phenyl)-7-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-5-methyl-quinazolin-4-amine

HRID 2281101Notes

Reaction equation

HRID 2281101 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23](Br)=[CH:24][C:25]=2[CH3:27])[N:20]=[CH:19][N:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:29][S:30]([CH3:33])(=[NH:32])=[O:31].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([N:32]=[S:30]([CH3:33])([CH3:29])=[O:31])=[CH:24][C:25]=2[CH3:27])[N:20]=[CH:19][N:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 123119Sulfoximine, S,S-dimethyl-HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 86718470N-(2-benzyloxy-4-fluoro-phenyl)-7-bromo-5-methyl-quinazolin-4-amine

Product 1

HCID 86718469N-(2-benzyloxy-4-fluoro-phenyl)-7-[[dimethyl(oxo)-lambda6-sulfanylidene]amino]-5-methyl-quinazolin-4-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

3.1 g (7 mmol) of N-(2-benzyloxy-4-fluoro-phenyl)-7-bromo-5-methyl-quinazolin-4-amine, 0.8 g (8.8 mmol) dimethylsulphoximine (IV.1), 0.4 g (1.4 mmol) 2-(di-t-butylphosphino) biphenyl, 0.5 g (0.5 mmol) Pd2dba3 and 1.0 g (10.2 mmol) sodium tert-butoxide in dioxane are heated to 80° C. for 4.5 h. After cooling to RT the reaction mixture is filtered, diluted with water and extracted with EtOAc. The organic layers are pooled, dried and evaporated. The residue is purified by FC giving rise to N-(2-benzyloxy-4-fluoro-phenyl)-7-[[dimethyl(oxo)-λ6-sulfanylidene]amino]-5-methyl-quinazolin-4-amine.

Workup

  1. filtrationis filtered
  2. additiondiluted with water
  3. extractionextracted with EtOAc
  4. customdried
  5. customevaporated
  6. customThe residue is purified by FC

Sources & evidence

ORD record
ord-0f60af2822a04e1fa1a2b5c25134b379
Source dataset
uspto-grants-2015_09
Patent number
US09139577B2

Reaction notes

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