1,3-Dichloro-5,5-dimethylhydantoin → 1-(4-(5-chlorothiazol-2-yl)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

HRID 1473627Notes

Reaction equation

HRID 1473627 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]2[S:10][CH:11]=[CH:12][N:13]=2)[CH:6]=[CH:5][C:4]=1[C:14]1[C:23]2[C:18](=[CH:19][C:20]([S:24]([NH:27][C:28]3[CH:33]=[CH:32][N:31]=[CH:30][N:29]=3)(=[O:26])=[O:25])=[CH:21][CH:22]=2)[CH:17]=[CH:16][N:15]=1.[Cl:34]N1C(C)(C)C(=O)N(Cl)C1=O>CO>[Cl:34][C:11]1[S:10][C:9]([C:7]2[CH:6]=[CH:5][C:4]([C:14]3[C:23]4[C:18](=[CH:19][C:20]([S:24]([NH:27][C:28]5[CH:33]=[CH:32][N:31]=[CH:30][N:29]=5)(=[O:26])=[O:25])=[CH:21][CH:22]=4)[CH:17]=[CH:16][N:15]=3)=[C:3]([O:2][CH3:1])[CH:8]=2)=[N:13][CH:12]=1

Participants

4

Reactant 2

HCID 83601,3-Dichloro-5,5-dimethylhydantoinHCID 866876951-(2-methoxy-4-(thiazol-2-yl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Product 1

HCID 866876971-(4-(5-chlorothiazol-2-yl)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamideYield 5.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1-(2-methoxy-4-(thiazol-2-yl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.100 g, 0.210 mmol) in 2 mL MeOH was treated with 1,3-dichloro-5,5-dimethylhydantoin (0.028 ml, 0.210 mmol) and was allowed to stir overnight at room temperature then was heated to reflux for two hours. LC/MS showed product, so the reaction mixture was concentrated. Purification of the crude residue by reverse phase column chromatography [Puriflash C18 30μ, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 1-(4-(5-chlorothiazol-2-yl)-2-methoxyphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (0.006 g, 0.012 mmol, 5.59% yield). 1H NMR (MeCN-d3) δ: 8.60-8.64 (m, 1H), 8.52-8.56 (m, 1H), 8.10-8.13 (m, 1H), 8.05-8.09 (m, 1H), 7.95-8.00 (m, 1H), 7.91-7.95 (m, 1H), 7.87-7.91 (m, 1H), 7.74-7.78 (m, 1H), 7.66-7.74 (m, 2H), 7.57-7.61 (m, 1H), 7.42-7.47 (m, 1H), 3.76 (s, 3H); (M+H)+=510.1.

Workup

  1. temperaturethen was heated
  2. temperatureto reflux for two hours
  3. concentrationso the reaction mixture was concentrated
  4. customPurification of the crude residue by reverse phase column chromatography [Puriflash C18 30μ, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-f99acb977d364bf58c05e5b805edea29
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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