Phosgene → 3-(3-Cyano-4-(isopropylsulfonyl)phenyl)-1,1-dimethylurea

HRID 1667613Notes

Reaction equation

HRID 1667613 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([S:10]([CH:13]([CH3:15])[CH3:14])(=[O:12])=[O:11])=[C:6]([CH:9]=1)[C:7]#[N:8].[C:16]([O-:19])(O)=O.[Na+].C(Cl)(Cl)=O.C[CH2:26][N:27](CC)[CH2:28]C.Cl.CNC>C(Cl)Cl.C1(C)C=CC=CC=1>[C:7]([C:6]1[CH:9]=[C:2]([NH:1][C:16](=[O:19])[N:27]([CH3:28])[CH3:26])[CH:3]=[CH:4][C:5]=1[S:10]([CH:13]([CH3:15])[CH3:14])(=[O:12])=[O:11])#[N:8]

Participants

8

Reactant 5

HCID 6371PhosgeneHCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 516892Sodium BicarbonateHCID 574482075-Amino-2-(isopropylsulfonyl)benzonitrile

Product 1

HCID 574482113-(3-Cyano-4-(isopropylsulfonyl)phenyl)-1,1-dimethylureaYield 50%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To 15C (67 mg, 0.30 mmol) in methylene chloride (2 mL) at 0° C. was added NaHCO3 (252 mg, 3 mmol) followed by a ca. 20% phosgene solution in toluene (0.3 mL). After stirring at that temperature for 2 h, the reaction was concentrated and diluted with methylene chloride (3 mL). To this solution was added Et3N (130 mg, 1.28 mmol) followed by dimethylamine hydrochloride (43 mg, 0.53 mmol) and the reaction was stirred overnight. The solution was loaded onto a silica gel column and purified via silica gel chromatography (0-80% ethyl acetate/hexane) to provide 16A (44 mg, 50%) and recovered starting material (15C) (20 mg). 16A: LC-MS: 296.02 (M+H)+.

Workup

  1. concentrationthe reaction was concentrated
  2. additiondiluted with methylene chloride (3 mL)
  3. stirringthe reaction was stirred overnight
  4. custompurified via silica gel chromatography (0-80% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-027a5ac4407e431f84282529838f03bc
Source dataset
uspto-grants-2011_10
Patent number
US08044242B2

Reaction notes

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