Diisopropylethylamine → tert-butyl 3-[(3-(benzyloxy)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzoyl)amino]-1H-pyrazole-1-carboxylate

HRID 20587Notes

Reaction equation

HRID 20587 reaction equation
CCN(C(C)C)C(C)C.[CH2:10]([O:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([O:27][C@@H:28]([CH3:41])[CH2:29][O:30][Si:31]([CH:38]([CH3:40])[CH3:39])([CH:35]([CH3:37])[CH3:36])[CH:32]([CH3:34])[CH3:33])[CH:26]=1)[C:21](O)=[O:22])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:66][C:67]1[CH:71]=[CH:70][N:69]([C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])[N:68]=1>CN(C=O)C.O>[CH2:10]([O:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([O:27][C@@H:28]([CH3:41])[CH2:29][O:30][Si:31]([CH:38]([CH3:40])[CH3:39])([CH:32]([CH3:34])[CH3:33])[CH:35]([CH3:37])[CH3:36])[CH:26]=1)[C:21]([NH:66][C:67]1[CH:71]=[CH:70][N:69]([C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])[N:68]=1)=[O:22])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

7

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 51358380tert-Butyl 3-amino-1H-pyrazole-1-carboxylateHCID 536296213-(benzyloxy)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzoic acid

Product 1

HCID 59346886tert-butyl 3-[(3-(benzyloxy)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzoyl)amino]-1H-pyrazole-1-carboxylateYield 30.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.21 mL, 1.2 mmol) was added to a solution of 3-(benzyloxy)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzoic acid (220 mg, 0.48 mmol), HATU (228 mg, 0.6 mmol), and tert-butyl 3-amino-1H-pyrazole-1-carboxylate (110 mg, 0.66 mmol) in DMF (2 mL) and the reaction mixture stirred at ambient temperature overnight. Water was added to the reaction mixture and extracted with ethyl acetate (3×25 mL). The combined organic extracts were separated and washed with 1M hydrochloric acid, saturated sodium hydrogen carbonate solution, saturated brine solution, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica, eluting with 0% to 50% ethyl acetate in hexanes, to give a clear oil (90 mg)

Workup

  1. extractionextracted with ethyl acetate (3×25 mL)
  2. customThe combined organic extracts were separated
  3. washwashed with 1M hydrochloric acid, saturated sodium hydrogen carbonate solution, saturated brine solution
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography on silica
  8. washeluting with 0% to 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-346dfd18640a41c7b33dbce80ca955be
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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