Ammonia → HCID 49764647, compound

HRID 1256258Notes

Reaction equation

HRID 1256258 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].C(Cl)Cl.C(O)(C(F)(F)F)=O.N>O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[C:7]3[NH:23][N:22]=[C:21]([NH:32][CH:33]4[CH2:34][CH2:35][N:36]([S:39]([NH2:42])(=[O:41])=[O:40])[CH2:37][CH2:38]4)[C:8]=3[N:9]=[C:10]([C:13]3[C:14]([F:20])=[CH:15][CH:16]=[CH:17][C:18]=3[F:19])[C:11]=2[CH:12]=1)#[N:2]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 66770647HCID 66770647, compound

Product 1

HCID 49764647HCID 49764647, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

306 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 20 ml of DCM. After cooling to 0° C. using an ice bath, 1.5 ml of TFA are added and the mixture is stirred at RT for 16 h. It is concentrated under RP and the solid obtained is taken up in 30 ml of water, neutralized with 2 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/NH4OH mixture (92.5/7.5/0.75 by volume). This gives 8 mg of 4-{[7-cyano-5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-c]isoquinolin-3-yl]amino}piperidine-1-sulphonamide. 1H NMR: 1.61-1.73 (m, 2 H) 2.09 (m, 2 H) 2.63-2.72 (m, 2 H) 3.47 (m, 2 H) 3.67-3.76 (m, 1 H) 6.13 (d, J=7.0 Hz, 1 H) 6.70 (s, 2 H) 7.34 (t, J=7.8 Hz, 2 H) 7.65-7.74 (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) 13.05 (s, 1 H).

Workup

  1. concentrationIt is concentrated under RP
  2. customthe solid obtained
  3. extractionIt is extracted with ethyl acetate
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under RP
  7. customThe product is purified by flash chromatography on silica gel (15-40 μm)
  8. washeluting with a DCM/methanol/NH4OH mixture (92.5/7.5/0.75 by volume)

Sources & evidence

ORD record
ord-808aec424a4a4c629099df43534245f2
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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