Ammonia → HCID 178513513, compound

HRID 1256252Notes

Reaction equation

HRID 1256252 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[C:7]3[C:8](=[C:21]([NH:32][CH:33]4[CH2:38][CH2:37][N:36]([S:39]([NH2:42])(=[O:41])=[O:40])[CH2:35][CH2:34]4)[N:22](COCC[Si](C)(C)C)[N:23]=3)[N:9]=[C:10]([C:13]3[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:14]=3[F:20])[C:11]=2[CH:12]=1)#[N:2].S(=O)(=O)(O)[OH:44].N>C1(C)C=CC=CC=1>[F:20][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]([F:19])[C:13]=1[C:10]1[C:11]2[CH:12]=[C:3]([C:1]([NH2:2])=[O:44])[CH:4]=[CH:5][C:6]=2[C:7]2=[N:23][NH:22][C:21]([NH:32][CH:33]3[CH2:34][CH2:35][N:36]([S:39](=[O:41])(=[O:40])[NH2:42])[CH2:37][CH2:38]3)=[C:8]2[N:9]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 1118Sulfuric AcidHCID 66770647HCID 66770647, compound

Product 1

HCID 178513513HCID 178513513, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

54 mg of 4-{[7-cyano-5-(2,6-difluorophenyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinolin-3-yl]amino}piperidine-1-sulphonamide are introduced into 0.5 ml of toluene. After cooling to 0° C. using an ice bath, 90 μl of 95% sulphuric acid are added and the mixture is stirred at RT for 24 h. It is cooled to 0° C. and neutralized with 9 ml of 7.5M aqueous ammonia solution. It is extracted with ethyl acetate, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with a DCM/methanol mixture (95/05 by volume). This gives 7 mg of 5-(2,6-difluorophenyl)-3-[(1-sulphamoylpiperidin-4-yl)amino]-2H-pyrazolo[4,3-c]isoquinoline-7-carboxamide (yellow solid). 1H NMR: 1.67 (m, 2 H) 2.11 (m, 2 H) 2.67 (m, 2 H) 3.47 (m, 2 H) 3.71 (m, 1 H) 6.01 (d, J=8.2 Hz, 1 H) 6.70 (broad s, 2 H) 7.33 (t, J=7.7 Hz, 2 H) 7.55 (broad s, 1 H) 7.68 (m, 1 H) 8.17 (broad s, 1 H) 8.22 (broad s, 1 H) 8.35 (broad d, J=8.5 Hz, 1 H) 8.45 (d, J=8.5 Hz, 1 H) 12.84 (s, 1 H).

Workup

  1. extractionIt is extracted with ethyl acetate
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under RP
  5. customThe product is purified by flash chromatography on silica gel (15-40 μm)
  6. washeluting with a DCM/methanol mixture (95/05 by volume)

Sources & evidence

ORD record
ord-1677dfb021964321bab7f565ecce4607
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

Loading…