p-Toluenesulfonic acid monohydrate → HCID 68656124, compound

HRID 502484Notes

Reaction equation

HRID 502484 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:39][CH2:40][CH:41]4[CH2:43][CH2:42]4)=[C:17]([NH:20][C:21](=[O:38])[CH:22]=[CH:23][CH2:24][N:25]([CH2:30][C:31]([O:33][C:34]([CH3:37])(C)[CH3:35])=[O:32])C[C@@H](O)C)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:39][CH2:40][CH:41]4[CH2:43][CH2:42]4)=[C:17]([NH:20][C:21](=[O:38])[CH:22]=[CH:23][CH2:24][N:25]4[CH2:35][C@H:34]([CH3:37])[O:33][C:31](=[O:32])[CH2:30]4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrate2×HCID 68656862HCID 68656862, compound

Product 1

HCID 68656124HCID 68656124, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 700 mg of 4-[(3-chloro-4-fluoro-phenyl)amino]-6-[(4-{N-[(tert.butyl-oxycarbonyl)methyl]-N-((S)-2-hydroxy-prop-1-yl)-amino}-1-oxo-2-buten-1-yl)amino]-7-cyclopropylmethoxy-quinazoline and 228 mg of p-toluenesulphonic acid hydrate in 20 ml of acetonitrile is refluxed for five hours. Then a further 200 mg of p-toluenesulphonic acid hydrate are added and the mixture is again refluxed for five hours. For working up the reaction mixture is evaporated to dryness. The flask residue is distributed between ethyl acetate and saturated sodium carbonate solution. The organic phase is separated off, washed with saturated sodium carbonate solution, water and saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. The oily residue is brought to crystallisation by stirring with 15 ml diethyl ether.

Workup

  1. temperatureis refluxed for five hours
  2. temperaturethe mixture is again refluxed for five hours
  3. customis evaporated to dryness
  4. customThe organic phase is separated off
  5. washwashed with saturated sodium carbonate solution, water and saturated sodium chloride solution
  6. dry with materialdried over magnesium sulphate
  7. customevaporated down
  8. customThe oily residue is brought to crystallisation

Sources & evidence

ORD record
ord-dc988545248049438a366ffb7080a35b
Source dataset
uspto-grants-2010_08
Patent number
US07776315B2

Reaction notes

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