Diisopropylethylamine → 3-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-N-(1-ethyl-1H-pyrazol-3-yl)-5-[(phenylmethyl)oxy]benzamide

HRID 20527

Reaction equation

HRID 20527 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([CH2:16][O:17][C:18]2[CH:19]=[C:20]([CH:24]=[C:25]([O:27][C@@H:28]([CH3:38])[CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH:26]=2)[C:21](O)=[O:22])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:63]([N:65]1[CH:69]=[CH:68][C:67]([NH2:70])=[N:66]1)[CH3:64]>CN(C=O)C>[CH3:35][C:34]([Si:31]([CH3:33])([CH3:32])[O:30][CH2:29][C@@H:28]([O:27][C:25]1[CH:24]=[C:20]([CH:19]=[C:18]([O:17][CH2:16][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:26]=1)[C:21]([NH:70][C:67]1[CH:68]=[CH:69][N:65]([CH2:63][CH3:64])[N:66]=1)=[O:22])[CH3:38])([CH3:37])[CH3:36]

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 121981091-ethyl-1H-pyrazol-3-amineHCID 536296343-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-5-[(phenylmethyl)oxy]benzoic acid

Product 1

HCID 593469163-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-N-(1-ethyl-1H-pyrazol-3-yl)-5-[(phenylmethyl)oxy]benzamideYield 65.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (3.11 mL, 18.03 mmol) was added to a solution of 3-{(phenylmethyl)oxy}-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid (3.00 g, 7.21 mmol), HATU (3.41 g, 9.01 mmol) and 1-ethyl-1H-pyrazol-3-amine [Chem. Heterocycl. Compd. (Engl. Transl.), 11, 1975, 212] (1.20 g, 10.8 mmol) in DMF (10 mL). The resulting mixture was stirred at ambient temperature for 3 hours. The DMF was removed in vacuo. The solvent was evaporated and the residue was dissolved in 5% w/v citric acid (50 mL), ethyl acetate (30 mL) and diethyl ether (30 mL) and the organic layer was further washed with sat. aqueous NaHCO3 (30 mL) and brine (30 mL). The organic layer was separated, then dried (MgSO4), filtered and evaporated. Purification by column chromatography, eluting with 1:5 to 1:2 ethyl acetate:hexanes, afforded the title compound as a colourless oil (2.40 g, 65%).

Workup

  1. customThe DMF was removed in vacuo
  2. customThe solvent was evaporated
  3. dissolutionthe residue was dissolved in 5%
  4. washthe organic layer was further washed with sat. aqueous NaHCO3 (30 mL) and brine (30 mL)
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by column chromatography
  10. washeluting with 1:5 to 1:2 ethyl acetate

Sources & evidence

ORD record
ord-0b1b374d0dd34a6a89f25d3edb4059c3
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Linked notes

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