Ammonia → HCID 49764525, compound

HRID 1256257Notes

Reaction equation

HRID 1256257 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]3[CH:23]=[N:22][NH:21][N:20]=3)[CH:15]=[CH:14][C:13]=2[C:12]2=[N:24][N:25](COCC[Si](C)(C)C)[C:26]([NH:27][CH:28]3[CH2:33][CH2:32][N:31]([S:34]([CH3:37])(=[O:36])=[O:35])[CH2:30][CH2:29]3)=[C:11]2[N:10]=1.C(Cl)Cl.C(O)(C(F)(F)F)=O.N>O>[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]3[CH:23]=[N:22][NH:21][N:20]=3)[CH:15]=[CH:14][C:13]=2[C:12]2[NH:24][N:25]=[C:26]([NH:27][CH:28]3[CH2:29][CH2:30][N:31]([S:34]([CH3:37])(=[O:36])=[O:35])[CH2:32][CH2:33]3)[C:11]=2[N:10]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 66770599HCID 66770599, compound

Product 1

HCID 49764525HCID 49764525, compoundYield 10.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

116 mg of 5-(2,6-difluorophenyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-7-(2H-1,2,3-triazol-4-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinolin-3-amine are introduced into 10 ml of DCM. After cooling to 0° C. using an ice bath, 1.1 ml of TFA are added and the mixture is stirred at RT for 5 h. It is concentrated under RP and the solid obtained is taken up in 60 ml of water, neutralized with 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 (92.5/7.5 by vol.), to give 10 mg of 5-(2,6-difluorophenyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-7-(2H-1,2,3-triazol-4-yl)-1H-pyrazolo[4,3-c]isoquinolin-3-amine (yellow solid). 1H NMR: 1.62-1.75 (m, 2 H) 2.10 (m, 2 H) 2.82-2.97 (m, 5 H) 3.57 (m, 2 H) 3.74-3.86 (m, 1 H) 6.04 (d, J=8.0 Hz, 1 H) 7.35 (t, J=8.0 Hz, 2 H) 7.63-7.75 (m, 1H) 8.13 (broad s, 1 H) 8.39 (broad d, J=8.6 Hz, 1 H) 8.45 (broad m, 1 H) 8.49 (d, J=8.6 Hz, 1 H) 12.77 (s, 1 H) 15.23 (broad m, 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 mixture (92.5/7.5 by vol.)

Sources & evidence

ORD record
ord-711884004f9d41328273adfb13f19077
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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