Trifluoroacetic acid → 8-(4-methoxybenzyl)-2-methyl-5,8-dihydro-4H-pyrazolo[3,4-c]thiazolo[5,4-f]isoquinoline

HRID 2383420Notes

Reaction equation

HRID 2383420 reaction equation
C[N:2](/[CH:4]=[C:5]1\[C:6](=O)[C:7]2[S:11][C:10]([CH3:12])=[N:9][C:8]=2[CH2:13][CH2:14]\1)[CH3:3].[CH3:16][O:17][C:18]1[CH:30]=[CH:29][C:21]([CH2:22][N:23]2C(N)=[CH:26][CH:25]=[N:24]2)=[CH:20][CH:19]=1.FC(F)(F)C(O)=O>O>[CH3:16][O:17][C:18]1[CH:30]=[CH:29][C:21]([CH2:22][N:23]2[C:3]3[N:2]=[CH:4][C:5]4[CH2:14][CH2:13][C:8]5[N:9]=[C:10]([CH3:12])[S:11][C:7]=5[C:6]=4[C:26]=3[CH:25]=[N:24]2)=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 31612621-((4-methoxyphenyl)methyl)-1H-pyrazol-5-amineHCID 59262908HCID 59262908, compound

Product 1

HCID 594908578-(4-methoxybenzyl)-2-methyl-5,8-dihydro-4H-pyrazolo[3,4-c]thiazolo[5,4-f]isoquinolineYield 19%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of (Z)-6-((dimethylamino)methylene)-2-methyl-5,6-dihydrobenzo[d]thiazol-7(4H)-one (3.5 g, 16.9 mmol) and 1-(4-methoxybenzyl)-1H-pyrazol-5-amine (3.5 g, 17.2 mmol) was added trifluoroacetic acid (2.3 mL, 29.2 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, 19%) as a solid. 1H NMR (CDCl3, 400 MHz): δ 7.86 (s, 1H), 7.76 (s, 1H), 7.36 (d, J=8.0 Hz, 2H), 6.82 (d, J=8.0 Hz, 2H), 5.59 (s, 2H), 3.75 (s, 3H), 3.17 (t, J=6.8 Hz, 2H), 3.09 (t, J=6.8 Hz, 2H), 2.77 (s, 3H); LCMS [M+H]: 363.

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-50b9bfe1126a4908bd57b6ef329191b3
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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