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

HRID 1990147

Reaction equation

HRID 1990147 reaction equation
CCN(C(C)C)C(C)C.[CH3:10][C:11]([Si:14]([CH3:38])([CH3:37])[O:15][CH2:16][C@@H:17]([O:19][C:20]1[CH:21]=[C:22]([CH:26]=[C:27]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:28]=1)[C:23]([OH:25])=O)[CH3:18])([CH3:13])[CH3:12].[NH2:39][C:40]1[CH:44]=[CH:43][N:42]([CH3:45])[N:41]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:10][C:11]([Si:14]([CH3:38])([CH3:37])[O:15][CH2:16][C@@H:17]([O:19][C:20]1[CH:21]=[C:22]([CH:26]=[C:27]([O:29][CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:28]=1)[C:23]([NH:39][C:40]1[CH:44]=[CH:43][N:42]([CH3:45])[N:41]=1)=[O:25])[CH3:18])([CH3:12])[CH3:13]

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 536296343-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-5-[(phenylmethyl)oxy]benzoic acid

Product 1

HCID 536296333-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(phenylmethyl)oxy]benzamideYield 64.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (4.06 g, 23.4 mmol) was added to a suspension of 3-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-5-[(phenylmethyl)oxy]benzoic acid (2.43 g, 5.84 mmol), 3-amino-1-methylpyrazole (0.85 g, 8.76 mmol) and HATU (4.66 g, 12.3 mmol) in DMF (50 mL) and stirred at ambient temperature for 16 hours. The resultant mixture was partially reduced in vacuo, poured onto water (100 mL) and extracted with diethyl ether (2×50 mL). The extracts were washed with water and brine then dried (MgSO4), filtered and reduced to an opaque gum which partially crystallized. The crude product was purified by column chromatography, eluting with 0-100% ethyl acetate in isohexane, to give the title compound as a colourless oil (1.87 g).

Workup

  1. additionpoured onto water (100 mL)
  2. extractionextracted with diethyl ether (2×50 mL)
  3. washThe extracts were washed with water and brine
  4. dry with materialthen dried (MgSO4)
  5. filtrationfiltered
  6. custompartially crystallized
  7. customThe crude product was purified by column chromatography
  8. washeluting with 0-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-0186dc34f79a408284d015bc86cb6127
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Linked notes

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