Trifluoroacetic acid → HCID 49764393, compound

HRID 1256246Notes

Reaction equation

HRID 1256246 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]([CH2:19][F: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: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]([CH2:19][F:20])[CH:15]=[CH:14][C:13]=2[C:12]2[NH:21][N:22]=[C:23]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([S:31]([CH3:34])(=[O:32])=[O:33])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66770368HCID 66770368, compound

Product 1

HCID 49764393HCID 49764393, compound

Reagents, catalysts & solvents 3

HCID 222AmmoniaSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 30 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 87 mg of [5-(2,6-difluorophenyl)-7-(fluoromethyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinolin-3-amine in 7 ml of DCM. After cooling to 0° C. using an ice bath, 0.85 ml of TFA is added and the mixture is stirred at RT for 3 h. The mixture is concentrated under RP and the solid obtained is taken up in 24 ml of water and 1.1 ml of 0.75M 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/MeOH mixture (95/05 by vol.). This gives 27 mg of [5-(2,6-difluorophenyl)-7-(fluoromethyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-1H-pyrazolo[4,3-c]isoquinolin-3-amine (yellow solid). 1H NMR; 1.67 (m, 2 H) 2.11 (m, 2 H) 2.87 (s, 3 H) 2.90 (m, 2 H) 3.56 (m, 2 H) 3.80 (broad m, 1 H) 5.58 (d, J=47.2 Hz, 2 H) 6.05 (broad d, J=8.0 Hz, 1 H) 7.33 (t, J=77 Hz, 2 H) 7.57-7.73 (m, 2 H) 7.95 (broad d, J=8.3 Hz, 1 H) 8.45 (d, J=8.3 Hz, 1 H) 12.81 (s, 1 H).

Workup

  1. customA 30 ml round-bottomed flask equipped with a magnetic stirrer and with a septum
  2. concentrationThe mixture is concentrated under RP
  3. customthe solid obtained
  4. extractionIt is extracted with ethyl acetate
  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 DCM/MeOH mixture (95/05 by vol.)

Sources & evidence

ORD record
ord-bdad167c78eb4a87ae7a5fd93bdca9b5
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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