Water → HCID 49764143, compound

HRID 1256236Notes

Reaction equation

HRID 1256236 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[NH:21][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.[NH4+]=[S:36].O>CO>[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](=[S:36])[NH2:20])[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

4

Reactant 2

HCID 962WaterHCID 49764269HCID 49764269, compound

Product 1

HCID 49764143HCID 49764143, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A microwave tube with a 5 ml capacity is charged with 45 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile, prepared in example 12, and 0.2 ml of a 20% aqueous solution of ammonium sulphide in 2 ml of methanol. The mixture is microwave-heated at 100° C. for 20 min (power set at 100 watts) and then poured into 50 ml of water and extracted with AcOEt. The organic phase is washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. The solid obtained is triturated in diisopropyl ether. The insolubles are filtered off under RP and dried under vacuum to give 36 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbothioamide (yellow solid). 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.66 (m, 2 H) 2.11 (m, 2 H) 2.88 (s, 3 H) 2.90 (m, 2 H) 3.56 (m, 2 H) 3.79 (m, 1H) 6.10 (d, J=8.3 Hz, 1 H) 7.33 (t, J=7.8 Hz, 2 H) 7.68 (m, 1 H) 8.18 (broad s, 1 H) 8.34 (dd, J=8.3, 1.5 Hz, 1 H) 8.40 (d, J=8.3 Hz, 1 H) 9.74 (broad s, 1 H) 10.01 (broad s, 1 H) 12.87 (broad m, 1 H) LC-MS-DAD-ELSD: 517 (+)=(M+H)(+).

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 solid obtained
  7. customis triturated in diisopropyl ether
  8. filtrationThe insolubles are filtered off under RP
  9. customdried under vacuum

Sources & evidence

ORD record
ord-d73c225165a443c8a14681a297eb9c75
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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