Trifluoroacetic acid → HCID 49764141, compound

HRID 1256230Notes

Reaction equation

HRID 1256230 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]#[CH:20])[CH:15]=[CH:14][C:13]=2[C:12]2=[N:21][N:22](COCC[Si](C)(C)C)[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.C(O)(C(F)(F)F)=O>C(Cl)Cl.O.N>[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]#[CH:20])[CH:15]=[CH:14][C:13]=2[C:12]2[NH:21][N:22]=[C:23]([NH:24][CH:25]3[CH2:26][CH2:27][N:28]([S:31]([CH3:34])(=[O:33])=[O:32])[CH2:29][CH2:30]3)[C:11]=2[N:10]=1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86664930HCID 86664930, compound

Product 1

HCID 49764141HCID 49764141, compound

Reagents, catalysts & solvents 3

HCID 222AmmoniaSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 30 ml round-bottomed flask equipped with a septum having a top-mounted argon intake is charged with 47 mg of 5-(2,6-difluorophenyl)-3-([1-(methylsulphonyl)piperidin-4-yl]amino}-2-{[2-(trimethylsilyl)ethoxy]methyl}-7-ethynyl-2H-pyrazolo[4,3-c]isoquinoline in 4 ml of DCM. After cooling to 0° C. using an ice bath, 0.47 ml of TFA is added and the mixture is stirred at RT for 3 h. It is concentrated under RP and the solid obtained is taken up in 25 ml of water and 0.75 ml of 0.75M aqueous ammonia solution. It is extracted with AcOEt, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with a mixture of DCM and methanol (92.5/7.5 by vol.). This gives 6 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-7-ethynyl-2H-pyrazolo[4,3-c]isoquinoline (yellow solid). MS (E/1); m/z=481 (M+); 1H NMR: 1.66 (m, 2 H) 2.11 (m, 2 H) 2.87 (s, 3 H) 2.91 (m, 2 H) 3.56 (m, 2 H) 3.79 (m, 1 H) 4.37 (s, 1 H) 6.10 (d, J=8.3 Hz, 1 H) 7.34 (t, J=7.9 Hz, 2 H) 7.65 (broad s, 1 H) 7.69 (m, 1 H) 7.97 (broad d, J=8.3 Hz, 1 H) 8.42 (d, J=8.3 Hz, 1 H) 12.88 (broad s, 1 H).

Workup

  1. customA 30 ml round-bottomed flask equipped with a septum
  2. concentrationIt is concentrated under RP
  3. customthe solid obtained
  4. extractionIt is extracted with AcOEt
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under RP
  8. customThe product is purified by flash chromatography on silica gel (15-40 μm)
  9. washeluting with a mixture of DCM and methanol (92.5/7.5 by vol.)

Sources & evidence

ORD record
ord-892d57c45ec94d46b852493fb755c020
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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