Dimethylsulphamoyl chloride → HCID 60036681, compound

HRID 1948949Notes

Reaction equation

HRID 1948949 reaction equation
Cl.[Cl:2][C:3]1[C:4]([F:28])=[C:5]([CH:25]=[CH:26][CH:27]=1)[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:23][CH3:24])=[C:14]([O:17][C@H:18]3[CH2:22][CH2:21][NH:20][CH2:19]3)[CH:15]=2)[N:10]=[CH:9][N:8]=1.[CH3:29][N:30]([CH3:35])[S:31](Cl)(=[O:33])=[O:32]>C(Cl)Cl.N1C=CC=CC=1.C(N(C(C)C)CC)(C)C>[Cl:2][C:3]1[C:4]([F:28])=[C:5]([CH:25]=[CH:26][CH:27]=1)[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:23][CH3:24])=[C:14]([O:17][C@H:18]3[CH2:22][CH2:21][N:20]([S:31](=[O:33])(=[O:32])[N:30]([CH3:35])[CH3:29])[CH2:19]3)[CH:15]=2)[N:10]=[CH:9][N:8]=1

Participants

6

Reactant 2

HCID 83372Dimethylsulphamoyl chlorideHCID 68520254HCID 68520254, compound

Product 1

HCID 60036681HCID 60036681, compoundYield 53.5%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 81531DiisopropylethylamineSolvent

Procedure

4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(3S)-pyrrolidin-3-yloxy]quinazoline hydrochloride (0.21 g, 0.49 mmole; prepared as described in Example 30-preparation of starting materials) was dissolved in a mixture of methylene chloride (4 ml), pyridine (1 ml) and di-isopropylethyl amine (0.17 ml) under a nitrogen atmosphere. Dimethylsulfamoyl chloride (0.08 ml, 0.75 mmole) was added to the stirred solution. After stirring overnight at ambient temperature, the reaction mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic layer was washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia)(98/2). The fractions containing the expected product were evaporated under vacuum and the residual gum was triturated with diethylether and evaporated to give the title product as a dry foam (0.13 g; 53%); 1H NMR Spectrum: (DMSO d6) 2.16-2.21 (m, 1H); 2.25-2.38 (m, 1H); 2.76 (s, 6H); 3.41-3.50 (m, 3H); 3.71 (dd, 1H); 3.93 (m, 3H); 5.18 (m, 1H); 7.15-7.35 (m, 2H); 7.44-7.55 (m, 2H); 7.78 (s, 1H); 8.37 (s, 1H); 9.59 (s, 1H); Mass Spectrum: (M+H) 496.

Workup

  1. customthe reaction mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography
  7. washeluting with methylene chloride/methanol (saturated with ammonia)(98/2)
  8. additionThe fractions containing the expected product
  9. customwere evaporated under vacuum
  10. customthe residual gum was triturated with diethylether
  11. customevaporated

Sources & evidence

ORD record
ord-7c3c6526cad345fbba79f43b9cbc8c4a
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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