Diisopropylethylamine → 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-[4-(methoxymethyl)-1,3-thiazol-2-yl]-5-[4-(methylsulfonyl)phenoxy]benzamide

HRID 20495

Reaction equation

HRID 20495 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]([OH:41])=O)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].CCN(C(C)C)C(C)C.[CH3:66][O:67][CH2:68][C:69]1[N:70]=[C:71]([NH2:74])[S:72][CH:73]=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:74][C:71]1[S:72][CH:73]=[C:69]([CH2:68][O:67][CH3:66])[N:70]=1)=[O:41])([C:28]([CH3:29])([CH3:31])[CH3:30])([CH3:26])[CH3:27]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 230925274-(Methoxymethyl)-1,3-thiazol-2-amineHCID 593469073-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]benzoic acid

Product 1

HCID 593468973-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-[4-(methoxymethyl)-1,3-thiazol-2-yl]-5-[4-(methylsulfonyl)phenoxy]benzamideYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (446 mg, 1.17 mmol) was added to 3-((1S)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]benzoic acid (450 mg, 0.94 mmol) followed by addition of DMF (4.5 mL), DIPEA (0.42 mL) and 4-(methoxymethyl)-1,3-thiazol-2-amine (160 mg, 1.11 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 (325 mg, 56%).

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-30e6221ea7f444b59ad313526a3e528b
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Linked notes

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