N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → HCID 178490986, compound

HRID 1473702Notes

Reaction equation

HRID 1473702 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][NH:8][C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Br:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([S:37](Cl)(=[O:39])=[O:38])=[CH:34][CH:35]=2)[CH:30]=[N:29][C:28]=1[OH:41]>C1COCC1>[Br:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([S:37]([N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:15][CH:14]=3)[C:9]3[S:10][CH:11]=[CH:12][N:13]=3)(=[O:38])=[O:39])=[CH:34][CH:35]=2)[CH:30]=[N:29][C:28]=1[OH:41]

Participants

5

Reactant 3

HCID 578640N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amineHCID 2733832Lithium HexamethyldisilazideHCID 178527424HCID 178527424, compound

Product 1

HCID 178490986HCID 178490986, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a vial charged with N-(4-methoxybenzyl)thiazol-2-amine (655 mg, 2.97 mmol) was added THF (6940 μl) and the mixture cooled in an ice water bath prior to the addition of lithium bis(trimethylsilyl)amide, 1.0M solution in tetrahydrofuran (3185 μl, 3.19 mmol), faster than drop wise. After 15 mins of stirring, a solution of 4-bromo-3-hydroxyisoquinoline-7-sulfonyl chloride (685 mg, 2.124 mmol) in THF (4 mL) was added drop wise (with 1 mL THF wash). The mixture was stirred for 1.5 hr (ice melt), LCMS indicated complete conversion to the desired product. The solution was added to ice, diluted with EtOAc and extracted with water and EtOAc. The combined organics were dried with Na2SO4, filtered, and dried under reduced pressure. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 60% EtOAc in hexane, to provide 4-bromo-3-hydroxy-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide. m/z (ESI) 506.0 (M+H)+

Workup

  1. temperaturethe mixture cooled in an ice water bath
  2. washdrop wise (with 1 mL THF wash)
  3. stirringThe mixture was stirred for 1.5 hr (ice melt), LCMS
  4. additionThe solution was added to ice
  5. additiondiluted with EtOAc
  6. extractionextracted with water and EtOAc
  7. dry with materialThe combined organics were dried with Na2SO4
  8. filtrationfiltered
  9. customdried under reduced pressure
  10. customThe crude material was absorbed onto a plug of silica gel
  11. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  12. washeluting with a gradient of 0% to 60% EtOAc in hexane

Sources & evidence

ORD record
ord-94d3cd2cdf364de7827083df35ef1ed8
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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