3-Chloropropanesulphonyl chloride → HCID 68522468, compound

HRID 1948913Notes

Reaction equation

HRID 1948913 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][S:5](Cl)(=[O:7])=[O:6].Cl.Cl.[NH:11]1[CH2:16][CH2:15][CH:14]([O:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][C:27]=2[O:28][CH3:29])[N:24]=[CH:23][N:22]=[C:21]3[NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=2[F:38])[CH2:13][CH2:12]1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[Cl:37][C:33]1[C:32]([F:38])=[C:31]([CH:36]=[CH:35][CH:34]=1)[NH:30][C:21]1[C:20]2[C:25](=[CH:26][C:27]([O:28][CH3:29])=[C:18]([O:17][CH:14]3[CH2:15][CH2:16][N:11]([S:5]([CH2:4][CH2:3][CH2:2][Cl:1])(=[O:7])=[O:6])[CH2:12][CH2:13]3)[CH:19]=2)[N:24]=[CH:23][N:22]=1

Participants

5

Reactant 3

HCID 154103-Chloropropanesulphonyl chlorideHCID 81531DiisopropylethylamineHCID 574768654-(3-Chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-4-yloxy)quinazoline dihydrochloride

Product 1

HCID 68522468HCID 68522468, compoundYield 69.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-chloropropanesulfonylchloride (174 mg) was added to a solution of 6-(piperidin-4-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline dihydrochloride (190 mg; starting material for Example 16) and diisopropylethylamine (140 mg) in methylene chloride (5 ml) at ambient temperature and the reaction mixture was stirred for 16 hours. The reaction mixture was adsorbed onto silica and the residue was purified by column chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 94/6). The fractions containing the expected product were combined and evaporated under vacuum to give 4-(3-chloro-2-fluoroanilino)-6-{1-[3-chloropropylsulfonyl]piperidin-4-yloxy}-7-methoxyquinazoline as a brown gum (0.15 g); Mass Spectrum: (M+H)+ 543.

Workup

  1. customthe residue was purified by column chromatography on silica eluting
  2. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 94/6)
  3. additionThe fractions containing the expected product
  4. customevaporated under vacuum

Sources & evidence

ORD record
ord-5d1dbc32d33a4868acaf657ed3576cb8
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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