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

HRID 548660Notes

Reaction equation

HRID 548660 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.[CH3:57][N:58]1[CH:62]=[CH:61][C:60]([NH2:63])=[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:63][C:60]1[CH:61]=[CH:62][N:58]([CH3:57])[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. 1-Methyl-1H-pyrazole-3-amine (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). 1H NMR δ (CDCl3): 1.05 (s, 18H), 1.05-1.1 (m, 3H), 1.3 (d, 3H), 3.7 (m, 1H), 3.8 (s, 3H), 3.9 (m, 1H), 4.5 (m, 1H), 5.1 (s, 2H), 6.7 (s, 1H), 6.8 (s, 1H), 7.0 (m, 2H), 7.1 (s, 1H), 7.3 (s, 1H), 7.35-7.5 (m, 5H), 8.5 (s, 1H). m/z 538 (M+H)+

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-839a016666e64233be41202b3cc2e1ad
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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