Hydrochloric Acid → 5-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde

HRID 1256249Notes

Reaction equation

HRID 1256249 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([CH:19]=[O:20])[CH:15]=[CH:14][C:13]=2[C:12]2[N:21](COCC[Si](C)(C)C)[N:22]=[C:23]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([S:31]([CH2:34][CH3:35])(=[O:33])=[O:32])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1.Cl>O>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([CH:19]=[O:20])[CH:15]=[CH:14][C:13]=2[C:12]2[NH:21][N:22]=[C:23]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([S:31]([CH2:34][CH3:35])(=[O:32])=[O:33])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 866649335-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde

Product 1

HCID 497643955-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A microwave tube with a maximum capacity of 20 ml is charged with 195 mg of 5-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde, and 10 ml of 5N aqueous HCl solution. The mixture is microwave-heated at 100° C. for 20 min and then poured into water and extracted with AcOEt. The organic phase is washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with a mixture of DCM and MeOH (95/5 by vol.). This gives 90 mg of 5-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde in the form of a yellow foam. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.23 (t, J=7.4 Hz, 3 H) 1.64 (m, 2 H) 2.10 (m, 2 H) 2.98 (m, 2H) 3.05 (q, J=7.4 Hz, 2 H) 3.62 (m, 2 H) 3.83 (m, 1 H) 6.18 (d, J=7.7 Hz, 1 H) 7.36 (t, J=7.8 Hz, 2 H) 7.71 (m, 1 H) 8.24 (broad s, 1 H) 8.34 (broad d, J=8.4 Hz, 1 H) 8.57 (d, J=8.4 Hz, 1 H) 10.11 (s, 1 H) 13.02 (s, 1 H). [M+H]+m/z=500.

Workup

  1. extractionextracted with AcOEt
  2. washThe organic phase is washed with saturated NaCl solution
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under RP
  6. customThe product is purified by flash chromatography on silica gel (15-40 μm)
  7. washeluting with a mixture of DCM and MeOH (95/5 by vol.)

Sources & evidence

ORD record
ord-eb1db752aa0c49cfbf1adee597011c3b
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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