Benzoic acid, 3-(chlorosulfonyl)- → 3-[(5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4,4]nonane-7-sulfonyl]-benzoic acid

HRID 1792875Notes

Reaction equation

HRID 1792875 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C@@:12]3([C@H:18]([C:19]4[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][CH:20]=4)[CH2:17][NH:16][CH2:15]3)[N:11]([CH3:27])[C:10]2=[O:28])[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl[S:30]([C:33]1[CH:34]=[C:35]([CH:39]=[CH:40][CH:41]=1)[C:36]([OH:38])=[O:37])(=[O:32])=[O:31].C(=O)(O)[O-].[Na+]>CC(C)=O.O>[C:23]([C:22]1[CH:21]=[CH:20][C:19]([C@H:18]2[C@:12]3([N:11]([CH3:27])[C:10](=[O:28])[N:9]([C:4]4[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=4)[C:13]3=[O:14])[CH2:15][N:16]([S:30]([C:33]3[CH:34]=[C:35]([CH:39]=[CH:40][CH:41]=3)[C:36]([OH:38])=[O:37])(=[O:32])=[O:31])[CH2:17]2)=[CH:26][CH:25]=1)#[N:24]

Participants

6

Reactant 3

HCID 77641Benzoic acid, 3-(chlorosulfonyl)-HCID 516892Sodium BicarbonateHCID 119947544-[(5S,9R)-3-(3,5-Dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-9-yl]-benzonitrile

Product 1

HCID 235404083-[(5S,9R)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4,4]nonane-7-sulfonyl]-benzoic acidYield 77%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

To a mixture of 4-[(5S,9R)-3-(3,5-Dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-9-yl]-benzonitrile (Example 15a) (0.11 g, 0.26 mmol) and (3-(Chlorosulfonyl)benzoic acid (0.058 g, 0.26 mmol) in acetone and water (1:1 mL) was added sodium bicarbonate at room temperature. The reaction mixture was stirred at room temperature for forty minutes, quenched by the slow addition of 1N hydrochloric acid (1 mL) and partitioned between DCM (2×20 mL) and brine (25 mL). The DCM layer was dried over sodium sulfate, concentrated and column purified using silica gel chromatography using DCM and MeOH to yield the titled compound (0.12 g). Retention time: 3.39 min. YMC S5 Combiscreen ODS 4.6×50 mm (4 minute gradient). Solvent A=10% MeOH, 90% water and 0.2% phosphoric acid. Solvent B=90% MeOH, 10% water and 0.2% phosphoric acid.

Workup

  1. customquenched by the slow addition of 1N hydrochloric acid (1 mL)
  2. custompartitioned between DCM (2×20 mL) and brine (25 mL)
  3. dry with materialThe DCM layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. customcolumn purified

Sources & evidence

ORD record
ord-fa608298f4e84e2c916e95bf0375dc9c
Source dataset
uspto-grants-2006_07
Patent number
US07078420B2

Reaction notes

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