Ammonia → HCID 49764524, compound

HRID 1256255Notes

Reaction equation

HRID 1256255 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:20]=[N:21][N:22](COCC[Si](C)(C)C)[CH:23]=3)[CH:15]=[CH:14][C:13]=2[C:12]2=[N:32][N:33](COCC[Si](C)(C)C)[C:34]([NH:35][CH:36]3[CH2:41][CH2:40][N:39]([S:42]([CH3:45])(=[O:44])=[O:43])[CH2:38][CH2:37]3)=[C:11]2[N:10]=1.C(Cl)Cl.C(O)(C(F)(F)F)=O.N>O>[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]3[CH:20]=[N:21][NH:22][CH:23]=3)[CH:15]=[CH:14][C:13]=2[C:12]2[NH:32][N:33]=[C:34]([NH:35][CH:36]3[CH2:37][CH2:38][N:39]([S:42]([CH3:45])(=[O:44])=[O:43])[CH2:40][CH2:41]3)[C:11]=2[N:10]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 66772338HCID 66772338, compound

Product 1

HCID 49764524HCID 49764524, compoundYield 10.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

73 mg of 5-(2,6-difluorophenyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-2-{[2-(trimethylsilyl)ethoxy]methyl}-7-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-4-yl)-2H-pyrazolo[4,3-c]isoquinolin-3-amine are introduced into 5 ml of DCM. After cooling to 0° C. using an ice bath, 0.58 ml of TFA is added and the mixture is stirred at RT for 5 h. The reaction mixture is concentrated under RP and the solid obtained is taken up in 23 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 DCM and then with a DCM/methanol mixture (90/10 by vol.), to give 5 mg of 5-(2,6-difluorophenyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-7-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]isoquinolin-3-amine (yellow solid). 1H NMR: 1.61-1.74 (m, 2 H) 2.06-2.16 (m, 2 H) 2.87 (s, 3 H) 2.89-2.95 (m, 2 H) 3.52-3.60 (m, 2 H) 3.75-3.84 (m, 1 H) 5.98 (d, J=8.2 Hz, 1 H) 7.31 (t, J=8.0 Hz, 2 H) 7.65-7.71 (m, 2 H) 7.82-7.88 (broad m, 1 H) 8.15-8.24 (broad m, 1 H) 8.18 (broad d, J=8.3 Hz, 1 H) 8.40 (d, J=8.3 Hz, 1 H) 12.66 (s, 1 H) 13.05 (broad s, 1 H).

Workup

  1. concentrationThe reaction mixture 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 DCM

Sources & evidence

ORD record
ord-04bf4bf05525440aaf6169cf89d029be
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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