Water → HCID 49764269, compound

HRID 1256242Notes

Reaction equation

HRID 1256242 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]([C:19]#[N: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]([CH3:34])(=[O:33])=[O:32])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1.O.[OH-].[Na+]>Cl>[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]([C:19]#[N: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]([CH3:34])(=[O:32])=[O:33])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 66774447HCID 66774447, compound

Product 1

HCID 49764269HCID 49764269, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
100 °C

Procedure

A microwave tube of maximum capacity 20 ml, equipped with a magnetic stirrer, is charged with 300 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-([2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile in 12 ml of 5N hydrochloric acid. The reaction mixture is microwave-heated at 100° C. for 5 min and then poured into 20 ml of water, brought to a pH of 7 by addition of 9.3N sodium hydroxide solution, and extracted with three times 20 ml of AcOEt. The combined organic phases are 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 AcOEt (50/50 by vol.), to give 130 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile (yellow solid). 1H NMR (400 MHz, DMSO-d6) 1.67 (m, 2 H) 2.11 (m, 2 H) 2.87 (s, 3 H) 2.90 (m, 2 H) 3.56 (m, 2 H) 3.80 (m, 1 H) 6.20 (broad d, J=7.7 Hz, 1 H) 7.34 (m, 2 H) 7.70 (m, 1 H) 8.18 (broad s, 1 H) 8.28 (broad d, J=8.6 Hz, 1 H) 8.56 (d, J=8.6 Hz, 1 H) 13.07 (s, 1H) LC-MS-DAD-ELSD: 483 (+)=(M+H)(+).

Workup

  1. customA microwave tube of maximum capacity 20 ml, equipped with a magnetic stirrer
  2. extractionextracted with three times 20 ml of AcOEt
  3. dry with materialThe combined organic phases are dried 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 AcOEt (50/50 by vol.)

Sources & evidence

ORD record
ord-4fecb97904cc48bb8a1f7f75450648d2
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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