Trifluoroacetic acid → HCID 59490646, compound

HRID 2383415Notes

Reaction equation

HRID 2383415 reaction equation
C[N:2](/[CH:4]=[C:5]1\[C:6](=O)[C:7]2[CH:8]=[N:9][N:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11]=2[CH2:12][CH2:13]\1)[CH3:3].[CH3:21][O:22][C:23]1[CH:35]=[CH:34][C:26]([CH2:27][N:28]2C(N)=[CH:31][CH:30]=[N:29]2)=[CH:25][CH:24]=1.FC(F)(F)C(O)=O>O>[CH3:21][O:22][C:23]1[CH:35]=[CH:34][C:26]([CH2:27][N:28]2[C:3]3[N:2]=[CH:4][C:5]4[CH2:13][CH2:12][C:11]5[N:10]([C:14]6[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=6)[N:9]=[CH:8][C:7]=5[C:6]=4[C:31]=3[CH:30]=[N:29]2)=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 31612621-((4-methoxyphenyl)methyl)-1H-pyrazol-5-amineHCID 21789945HCID 21789945, compound

Product 1

HCID 59490646HCID 59490646, compoundYield 52.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of (Z)-5-((dimethylamino)methylene)-1-phenyl-6,7-dihydro-1H-indazol-4(5H)-one (1 g, 3.74 mmol) and 1-(4-methoxybenzyl)-1H-pyrazol-5-amine (3.5 g, 17.2 mmol) was added trifluoroacetic acid (0.8 mL, 10.3 mmol). The reaction mixture was heated at 100° C. for 2 hours. The reaction mixture was then poured into ice-cooled water (100 mL) and extracted with dichloromethane (3×75 mL). The combined organic extracts were dried using sodium sulfate and concentrated under reduced pressure to give a dark residue. The crude product was purified by flash column chromatography (SiO2, gradient from 100% chloroform to 2% methanol in chloroform) to a residue, which was further purified by crystallization from methanol and isopropanol to give the pure desired product (0.8 g, 15%) as a solid. 1H NMR (CDCl3, 400 MHz): δ 8.33 (s, 1H), 7.87 (s, 1H), 7.78 (s, 1H), 7.55-7.49 (m, 4H), 7.41-7.39 (m, 1H), 7.38 (d, J=8.4 Hz, 2H), 6.83 (d, J=8.4 Hz, 2H), 5.66 (s, 2H), 3.75 (s, 3H), 3.14-3.09 (m, 4H); LCMS [M+H]: 408.

Workup

  1. additionThe reaction mixture was then poured into ice-
  2. extractionextracted with dichloromethane (3×75 mL)
  3. customThe combined organic extracts were dried
  4. concentrationconcentrated under reduced pressure
  5. customto give a dark residue
  6. customThe crude product was purified by flash column chromatography (SiO2, gradient from 100% chloroform to 2% methanol in chloroform) to a residue, which
  7. customwas further purified by crystallization from methanol and isopropanol

Sources & evidence

ORD record
ord-7d9e08d3e466432e94fd39c41898fd89
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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