Diisopropylethylamine → 3-(benzyloxy)-N-(1-methyl-1H-pyrazol-3-yl)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzamide

HRID 1989885Notes

Reaction equation

HRID 1989885 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:25]([O:32][C:33]1[CH:34]=[C:35]([CH:39]=[C:40]([O:42][C@@H:43]([CH3:56])[CH2:44][O:45][Si:46]([CH:53]([CH3:55])[CH3:54])([CH:50]([CH3:52])[CH3:51])[CH:47]([CH3:49])[CH3:48])[CH:41]=1)[C:36]([OH:38])=O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[NH2:57][C:58]1[CH:62]=[CH:61][N:60]([CH3:63])[N:59]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:25]([O:32][C:33]1[CH:34]=[C:35]([CH:39]=[C:40]([O:42][C@@H:43]([CH3:56])[CH2:44][O:45][Si:46]([CH:53]([CH3:55])[CH3:54])([CH:47]([CH3:49])[CH3:48])[CH:50]([CH3:52])[CH3:51])[CH:41]=1)[C:36]([NH:57][C:58]1[CH:62]=[CH:61][N:60]([CH3:63])[N:59]=1)=[O:38])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1372541-Methyl-3-aminopyrazoleHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 536296213-(benzyloxy)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzoic acid

Product 1

HCID 536296203-(benzyloxy)-N-(1-methyl-1H-pyrazol-3-yl)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzamideYield 78.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

HATU (23.5 g, 61.8 mmol) was added to 3-(benzyloxy)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzoic acid (23.6 g, 51.5 mmol), followed by addition of DMF (140 mL), and cooled to 0° C. 3-Amino-1-methylpyrazole (6.00 g. 61.8 mmol) was added followed by DIPEA (21.3 mL) and the reaction was stirred under argon at 0° C. for 3 hours. The solvent was evaporated and the residue was dissolved in ethyl acetate (500 mL) and washed with citric acid solution (200 mL), sodium hydrogen carbonate solution (150 mL), and saturated brine solution (2×150 mL). The organic layer was separated and dried (MgSO4), filtered and evaporated. Purification by column chromatography, eluting with 1:4 to 1:1 ethyl acetate:hexanes, afforded the title compound as a colourless oil (21.7 g).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in ethyl acetate (500 mL)
  3. washwashed with citric acid solution (200 mL), sodium hydrogen carbonate solution (150 mL), and saturated brine solution (2×150 mL)
  4. customThe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by column chromatography
  9. washeluting with 1:4 to 1:1 ethyl acetate

Sources & evidence

ORD record
ord-aae36b34405d4d0a86ee95db3f727b35
Source dataset
uspto-grants-2010_01
Patent number
US07642263B2

Reaction notes

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