2-Aminothiazole → 3-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]-N-1,3-thiazol-2-ylbenzamide

HRID 20487

Reaction equation

HRID 20487 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Si:25]([O:32][CH2:33][C@H:34]([CH3:56])[O:35][C:36]1[CH:37]=[C:38]([CH:42]=[C:43]([O:45][C:46]2[CH:51]=[CH:50][C:49]([S:52]([CH3:55])(=[O:54])=[O:53])=[CH:48][CH:47]=2)[CH:44]=1)[C:39](O)=[O:40])([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].[NH2:57][C:58]1[S:59][CH:60]=[CH:61][N:62]=1>CN(C=O)C>[Si:25]([O:32][CH2:33][C@H:34]([CH3:56])[O:35][C:36]1[CH:37]=[C:38]([CH:42]=[C:43]([O:45][C:46]2[CH:47]=[CH:48][C:49]([S:52]([CH3:55])(=[O:53])=[O:54])=[CH:50][CH:51]=2)[CH:44]=1)[C:39]([NH:57][C:58]1[S:59][CH:60]=[CH:61][N:62]=1)=[O:40])([C:28]([CH3:31])([CH3:29])[CH3:30])([CH3:26])[CH3:27]

Participants

5

Reactant 3

HCID 21552-AminothiazoleHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 593469073-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]benzoic acid

Product 1

HCID 593468793-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]-N-1,3-thiazol-2-ylbenzamideYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (513 mg, 1.35 mmol) was added to 3-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]benzoic acid (520 mg, 1.08 mmol) followed by addition of DMF (5 mL), disopropylethylamine (0.48 mL) and 2-aminothiazole (135 mg, 1.35 mmol) and the reaction was stirred under argon for 4 h. The solvent was evaporated and the residue was dissolved in saturated aqueous sodium hydrogencarbonate (30 mL) and ethyl acetate (50 mL). The organic layer was separated, washed with saturated aqueous ammonium chloride (30 mL) then dried (MgSO4), filtered and evaporated. Purification by column chromatography, eluting with 1:2 to 2:1 ethyl acetate:hexanes, afforded the title compound as a colourless oil (425 mg, 70%).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in saturated aqueous sodium hydrogencarbonate (30 mL)
  3. customThe organic layer was separated
  4. washwashed with saturated aqueous ammonium chloride (30 mL)
  5. dry with materialthen dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by column chromatography
  9. washeluting with 1:2 to 2:1 ethyl acetate

Sources & evidence

ORD record
ord-dd289d532c2d443f9197e77eb9b1b981
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Linked notes

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