Diisopropylethylamine → 7-(3,4-dichlorophenyl)-6,7-dihydro-3H-benzo[f]pyrazolo[3,4-c]isoquinoline

HRID 2383399Notes

Reaction equation

HRID 2383399 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:18][C:17]3[CH:16]=[N:15][C:14]4[N:19](CC5C=CC(OC)=CC=5)[N:20]=[CH:21][C:13]=4[C:12]=3[C:11]3[CH:31]=[CH:32][CH:33]=[CH:34][C:10]2=3)[CH:5]=[CH:6][C:7]=1[Cl:8].ClC1C=C(C2C3C(=CC=CC=3)C(=O)/C(=C/N(C)C)/C2)C=CC=1Cl.Cl.COC1C=CC(CN2C(N)=CC=N2)=CC=1.CCN(C(C)C)C(C)C>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:18][C:17]3[CH:16]=[N:15][C:14]4[NH:19][N:20]=[CH:21][C:13]=4[C:12]=3[C:11]3[CH:31]=[CH:32][CH:33]=[CH:34][C:10]2=3)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5914006(2E)-4-(3,4-dichlorophenyl)-2-(dimethylaminomethylidene)-3,4-dihydronaphthalen-1-oneHCID 429375131-(4-methoxybenzyl)-1H-pyrazol-5-amine hydrochlorideHCID 674251267-(3,4-dichlorophenyl)-3-(4-methoxybenzyl)-6,7-dihydro-3H-benzo[f]pyrazolo[3,4-c]isoquinoline

Product 1

HCID 594907547-(3,4-dichlorophenyl)-6,7-dihydro-3H-benzo[f]pyrazolo[3,4-c]isoquinolineYield 53%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
110 °C

Procedure

Synthesis of 7-(3,4-dichlorophenyl)-3-(4-methoxybenzyl)-6,7-dihydro-3H-benzo[f]pyrazolo[3,4-c]isoquinoline. To the mixture of (E)-4-(3,4-dichlorophenyl)-2-((dimethylamino)methylene)-3,4-dihydronaphthalen-1(2H)-one (0.20 g, 0.58 mmol) and 1-(4-methoxybenzyl)-1H-pyrazol-5-amine hydrochloride (0.14 g, 0.58 mmol) was added glacial acetic acid (5 mL) and Hunig's Base (0.4 mL). The mixture was heated at 110° C. for 1 hour, then transferred to microwave vial and heated at 220° C. for 90 minutes. The reaction mixture was evaporated and dissolved in dichloromethane (100 mL), washed with water (30 mL), brine (30 mL), dried over sodium sulfate and concentrated to dryness. The crude was purified by flash column chromatography (SiO2, 10% EtOAc in hexane) to give the pure desired product as a brown solid (0.15 g, 53%). M.p.=76-78° C.; 1H NMR (CDCl3, 400 MHz) δ 9.53 (d, J=8 Hz, 1H), 8.32 (s, 1H), 8.02 (s, 1H), 7.54 (t, J=6.8 Hz, 1H), 7.45 (t, J=8 Hz, 1H), 7.35-7.26 (m, 4H), 7.06 (d, J=8 Hz, 1H), 6.96 (d, J=8 HZ, 1H), 6.843 (d, J=7.2 Hz, 2H), 4.28 (t, J=8 Hz, 1H), 4.17 (s, 2H), 3.77 (s, 3H), 3.29-3.26 (m, 2H); LCMS: 486 [M+1].

Workup

  1. temperatureheated at 220° C. for 90 minutes
  2. customThe reaction mixture was evaporated
  3. dissolutiondissolved in dichloromethane (100 mL)
  4. washwashed with water (30 mL), brine (30 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customThe crude was purified by flash column chromatography (SiO2, 10% EtOAc in hexane)

Sources & evidence

ORD record
ord-47f87d4dce054707b62a9d324c10ffa0
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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