Diisopropylethylamine → N-(1-ethyl-1H-pyrazol-3-yl)-3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]benzamide

HRID 548680Notes

Reaction equation

HRID 548680 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][O:26][CH2:27][C@@H:28]([O:30][C:31]1[CH:32]=[C:33]([CH:37]=[C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:39]=1)[C:34]([OH:36])=O)[CH3:29].[CH2:48]([N:50]1[CH:54]=[CH:53][C:52]([NH2:55])=[N:51]1)[CH3:49].CCN(C(C)C)C(C)C>C(OCC)(=O)C.CN(C=O)C>[CH2:48]([N:50]1[CH:54]=[CH:53][C:52]([NH:55][C:34](=[O:36])[C:33]2[CH:37]=[C:38]([O:40][CH2:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH:39]=[C:31]([O:30][C@@H:28]([CH3:29])[CH2:27][O:26][CH3:25])[CH:32]=2)=[N:51]1)[CH3:49]

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 121981091-ethyl-1H-pyrazol-3-amineHCID 59127150Benzoic acid, 3-[(1S)-2-methoxy-1-methylethoxy]-5-(phenylmethoxy)-

Product 1

HCID 53629645N-(1-ethyl-1H-pyrazol-3-yl)-3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]benzamideYield 90.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

HATU (23.5 g, 61.83 mmol) was added to 3-[(1S)-2-methoxy-(1-methylethyl)oxy]-5-{[phenylmethyl]oxy}benzoic acid (16.28 g, 51.53 mmol) followed by addition of DMF (140 mL) and cooled to 0° C. 1-Ethyl-1H-pyrazol-3-amine (6.86 g, 61.8 mmol) was added followed by DIPEA (21.3 mL) and the reaction stirred under argon, at 0° C., for 3 hours. The solvent volume was reduced and the residue was dissolved in ethyl acetate (500 mL), washed with citric acid (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 on silica, eluting with 10-50% ethyl acetate in hexanes, afforded the title compound as a pale yellow oil (19.1 g). 1H NMR δ (CDCl3): 1.23 (d, 3H), 1.38 (t, 3H), 3.33 (s, 3H), 3.42 (dd, 1H), 3.50 (dd, 1H), 3.97 (q, 2H), 4.49 (sextet, 1H), 4.99 (s, 2H), 6.66 (t, 1H), 6.75 (d, 1H), 6.98 (s, 1H), 7.02 (s, 1H), 7.26 (d, 1H), 7.28-7.37 (m, 5H), 8.58 (s, 1H); m/z 410 (M+H)+

Workup

  1. washwashed with citric acid (200 mL), sodium hydrogen carbonate solution (150 mL) and saturated brine solution (2×150 mL)
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customPurification by column chromatography on silica
  7. washeluting with 10-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-21e6d629e239405781302d7fe40f56ce
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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