Water → HCID 86687752, compound

HRID 1473674Notes

Reaction equation

HRID 1473674 reaction equation
C([S:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([C:20]3[CH:25]=[C:24]([F:26])[C:23]([CH:27]([F:29])[F:28])=[CH:22][C:21]=3[O:30][CH3:31])=[N:14][C:15]([CH3:19])=[N:16]2)=[CH:11][CH:10]=1)C1C=CC=CC=1.CC(O)=O.[OH2:36].[Cl:37]N1C(C)(C)C(=O)N(Cl)C1=O.[OH2:48]>C(Cl)Cl>[F:28][CH:27]([F:29])[C:23]1[C:24]([F:26])=[CH:25][C:20]([C:13]2[C:12]3[C:17](=[CH:18][C:9]([S:8]([Cl:37])(=[O:48])=[O:36])=[CH:10][CH:11]=3)[N:16]=[C:15]([CH3:19])[N:14]=2)=[C:21]([O:30][CH3:31])[CH:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 83601,3-Dichloro-5,5-dimethylhydantoinHCID 21899381Acetic acid--water (1/1)HCID 86687753HCID 86687753, compound

Product 1

HCID 86687752HCID 86687752, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 7-(benzylthio)-4-(4-(difluoromethyl)-5-fluoro-2-methoxyphenyl)-2-methylquinazoline (0.995 g, 2.259 mmol) in 22 mL DCM and 0.44 mL (3:2 HOAc/water) solution was cooled to 0° C. and was treated with 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione (0.890 g, 4.52 mmol). After stirring for 15 minutes, LC/MS showed mostly product, so the reaction mixture was diluted with water. The layers were separated, and the organics were dried over MgSO4 and concentrated. Purification of the crude residue by silica gel column chromatography (0-75% EtOAc/heptane) gave 4-(4-(difluoromethyl)-5-fluoro-2-methoxyphenyl)-2-methylquinazoline-7-sulfonyl chloride (0.550 g, 1.320 mmol, 58.4% yield) white solid. (M+H)+=417.0.

Workup

  1. customThe layers were separated
  2. dry with materialthe organics were dried over MgSO4
  3. concentrationconcentrated
  4. customPurification of the crude residue by silica gel column chromatography (0-75% EtOAc/heptane)

Sources & evidence

ORD record
ord-d189b98e12e442c5a6920a13aaca68d0
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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