Trifluoroacetic acid → HCID 136336750, compound

HRID 1256219Notes

Reaction equation

HRID 1256219 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]([CH:19]=[N:20][OH:21])[CH:15]=[CH:14][C:13]=2[C:12]2[N:22](COCC[Si](C)(C)C)[N:23]=[C:24]([NH:25][CH:26]3[CH2:31][CH2:30][N:29]([S:32]([CH3:35])(=[O:34])=[O:33])[CH2:28][CH2:27]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]([CH:19]=[N:20][OH:21])[CH:15]=[CH:14][C:13]=2[C:12]2[NH:22][N:23]=[C:24]([NH:25][CH:26]3[CH2:31][CH2:30][N:29]([S:32]([CH3:35])(=[O:33])=[O:34])[CH2:28][CH2:27]3)[C:11]=2[N:10]=1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 136391029HCID 136391029, compound

Product 1

HCID 136336750HCID 136336750, compoundYield 44.1%

Reagents, catalysts & solvents 3

HCID 222AmmoniaSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 50 ml round-bottomed flask equipped with a septum having a top-mounted argon intake is charged with 180 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde oxime in 15 ml of DCM. After cooling to 0° C. using an ice bath, 1.8 ml of TFA are added and the mixture is stirred at RT for 6 h. The mixture is concentrated under RP and the solid obtained is taken up in 50 ml of water and 2 ml of 0.75M aqueous ammonia solution. It is extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. Chromatography on silica gel (20-45 μm), eluting with a mixture of DCM and methanol (92.5/7.5 by vol.), gives 63 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde oxime (lemon yellow solid). MS (E/I): m/z=500 (M+); 1H NMR: 1.67 (m, 2H); 2.11 (m, 2H); 2.87 (s, 3H); 2.89 (m, 2H); 3.56 (m, 2H); 3.79 (m, 1H); 6.06 (d, J=7.8 Hz, 1H); 7.32 (broad t, J=7.6 Hz, 2H); 7.67 (m, 1H); 7.84 (broad s, 1H); 8.14 (broad d, J=8.5 Hz, 1H); 8.30 (s, 1H); 8.41 (d, J=8.5 Hz, 1H); 11.43 (s, 1H); 12.81 (s, 1H).

Workup

  1. customA 50 ml round-bottomed flask equipped with a septum
  2. concentrationThe mixture is concentrated under RP
  3. customthe solid obtained
  4. extractionIt is extracted with AcOEt
  5. washwashed with saturated NaCl solution
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under RP
  9. washChromatography on silica gel (20-45 μm), eluting with a mixture of DCM and methanol (92.5/7.5 by vol.)

Sources & evidence

ORD record
ord-51a3ba51f96e4f1186757ab8c0e0bc06
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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