Sulfuryl chloride → 3-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-(methylsulfonyl)azetidine-3-carboxamide

HRID 1867774Notes

Reaction equation

HRID 1867774 reaction equation
[CH:1](N(C(C)C)CC)(C)C.[S:10](Cl)(Cl)(=[O:12])=[O:11].[Cl:15][C:16]1[C:17]([F:45])=[C:18]([NH:22][C:23]2[C:32]3[C:27](=[CH:28][C:29]([O:43][CH3:44])=[C:30]([CH2:33][N:34]([CH3:42])[C:35]4([C:39]([NH2:41])=[O:40])[CH2:38][NH:37][CH2:36]4)[CH:31]=3)[N:26]=[CH:25][N:24]=2)[CH:19]=[CH:20][CH:21]=1>C(Cl)Cl>[Cl:15][C:16]1[C:17]([F:45])=[C:18]([NH:22][C:23]2[C:32]3[C:27](=[CH:28][C:29]([O:43][CH3:44])=[C:30]([CH2:33][N:34]([CH3:42])[C:35]4([C:39]([NH2:41])=[O:40])[CH2:38][N:37]([S:10]([CH3:1])(=[O:12])=[O:11])[CH2:36]4)[CH:31]=3)[N:26]=[CH:25][N:24]=2)[CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 24648Sulfuryl chlorideHCID 81531DiisopropylethylamineHCID 579798103-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide

Product 1

HCID 579798973-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-(methylsulfonyl)azetidine-3-carboxamideYield 33%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Diisopropylethylamine (72 μl, 0.41 mmol) then sulfonyl chloride (11 μl, 0.14 mmol) were added to a solution of the hydrochloride salt of 3-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]azetidine-3-carboxamide (Example 74) (60 mg, 0.12 mmol) in CH2Cl2 (1 ml) at 0° C. After 1 hour, the reaction mixture was diluted in 50 ml CH2Cl2 and washed with water. The organic layer was dried on MgSO4, then concentrated under reduced pressure. The crude product was purified on preparative HPLC (standard basic condition) to give the title product (20 mg, 33%) as a white powder; 1H NMR Spectrum: (CDCl3) 2.17 (s, 3H), 3.05 (s, 3H), 3.61 (s, 2H), 3.97 (s, 3H), 4.03 (d, 2H), 4.11 (s, 2H), 7.21 (s, 1H), 7.30 (m, 1H), 7.48 (m, 2H), 7.60 (brs, 2H), 8.38 (s, 1H), 8.44 (s, 1H), 9.75 (s, 1H); Mass Spectrum: (M+H)+ 523.

Workup

  1. washwashed with water
  2. customThe organic layer was dried on MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified on preparative HPLC (standard basic condition)

Sources & evidence

ORD record
ord-08dd85a40f854ee19fee25fda69f199a
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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