Water → N-[(1R)-2-Hydroxy-1-phenylethyl]-5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carboxamide

HRID 2400580Notes

Reaction equation

HRID 2400580 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:15]([OH:17])=O)[CH:3]=1.N1(OC(N(C)C)=[N+](C)C)[C:22]2[N:23]=[CH:24][CH:25]=[CH:26][C:21]=2N=N1.F[P-](F)(F)(F)(F)F.C(N([CH2:47][CH3:48])CC)C.O.CN([CH:53]=[O:54])C>>[OH:54][CH2:53][C@H:24]([NH:23][C:15]([C:4]1[CH:3]=[C:2]([CH3:1])[N:6]([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([CH3:14])=[CH:12][CH:13]=2)[N:5]=1)=[O:17])[C:25]1[CH:26]=[CH:21][CH:22]=[CH:48][CH:47]=1

Participants

6

Reactant 5

HCID 962WaterHCID 6228Dimethylformamide2×HCID 8471TriethylamineHCID 27470481-(4-Methylbenzyl)-5-methyl-1H-pyrazole-3-carboxylic acid2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 59504667N-[(1R)-2-Hydroxy-1-phenylethyl]-5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carboxamideYield 97%

Procedure

To a solution of 5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carboxylic acid (Intermediate B, 250 mg, 1.08 mmol) in DMF (5 mL) was added O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium PF6 (619 mg, 1.63 mmol), and the mixture was stirred at rt for 30 min. To this reaction mixture was then added (D)-(−)-2-phenylglycinol (198 mg, 2.17 mmol) in DMF (5 mL) followed by triethylamine (1.21 mL, 8.69 mmol), and the mixture was stirred at rt for 16 h. Water (10 mL) was added, and the mixture was extracted with ethyl acetate (1×25 mL), dried (Na2SO4), filtered, and concentrated to dryness. The crude material was purified with an ISCO CombiFlash Companion using gradient elution from 20% to 100% EtOAc in hexanes to afford the title compound as a white solid (370 mg, 97%): 1H NMR (300 MHz, DMSO-d6) δ 8.14 (d, 1H), 7.19-7.34 (m, 5H), 7.12 (d, 2H), 6.98 (d, 2H), 6.44 (s, 1H), 5.32 (s, 2H), 4.93-4.96 (m, 2H), 3.64-3.68 (m, 2H), 2.25 (s, 3H), 2.17 (s, 3H); ES-MS m/z 350.11, HPLC RT (Method B) 3.32 min.

Workup

  1. stirringthe mixture was stirred at rt for 16 h
  2. extractionthe mixture was extracted with ethyl acetate (1×25 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe crude material was purified with an ISCO CombiFlash Companion
  7. washelution from 20% to 100% EtOAc in hexanes

Sources & evidence

ORD record
ord-7935dc0445c24ee9a24c108ff9abc3e3
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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