Trifluoroacetic acid → HCID 49764142, compound

HRID 1256235Notes

Reaction equation

HRID 1256235 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]([O:21][CH3:22])=[O:20])[CH:15]=[CH:14][C:13]=2[C:12]2[N:23](COCC[Si](C)(C)C)[N:24]=[C:25]([NH:26][CH:27]3[CH2:32][CH2:31][N:30]([S:33]([CH3:36])(=[O:35])=[O:34])[CH2:29][CH2:28]3)[C:11]=2[N:10]=1.FC1C=CC=C(F)C=1C1C2C=C(C(OC)=O)C=CC=2C2=NN(COCC[Si](C)(C)C)C(NC3CCN(S(C)(=O)=O)CC3)=C2N=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.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]([O:21][CH3:22])=[O:20])[CH:15]=[CH:14][C:13]=2[C:12]2[NH:23][N:24]=[C:25]([NH:26][CH:27]3[CH2:28][CH2:29][N:30]([S:33]([CH3:36])(=[O:35])=[O:34])[CH2:31][CH2:32]3)[C:11]=2[N:10]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 67494319HCID 67494319, compoundHCID 67494479HCID 67494479, compound

Product 1

HCID 49764142HCID 49764142, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 25 ml round-bottomed flask equipped with a magnetic stirrer is charged with 46 mg of the mixture of methyl 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxylate and methyl 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinoline-7-carboxylate obtained in step 9 in 5 ml of DCM. After cooling to 0° C. using an ice bath, 0.5 ml of TFA are added and the mixture is stirred at RT for 18 h. It is concentrated under RP and the solid obtained is taken up in 20 ml of water and extracted with three times 20 ml of AcOEt. The organic phase is 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 mixture of DCM/AcOEt (50/50 by vol.), to give 12 mg of methyl 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxylate (yellow solid). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.67 (m, 2 H) 2.11 (m, 2 H) 2.88 (s, 3 H) 2.92 (m, 2 H) 3.56 (m, 2 H) 3.80 (m, 1 H) 3.87 (s, 3 H) 6.16 (d, J=7.7 Hz, 1 H) 7.37 (m, 2 H) 7.71 (m, 1 H) 8.23 (broad s, 1 H) 8.42 (broad d, J=8.5 Hz, 1 H) 8.54 (d, J=8.5 Hz, 1 H) 13.01 (s, 1 H). LC-MS-DAD-ELSD: 516 (+)=(M+H)(+).

Workup

  1. customA 25 ml round-bottomed flask equipped with a magnetic stirrer
  2. concentrationIt is concentrated under RP
  3. customthe solid obtained
  4. extractionextracted with three times 20 ml of AcOEt
  5. dry with materialThe organic phase is dried 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 DCM
  10. additionwith a mixture of DCM/AcOEt (50/50 by vol.)

Sources & evidence

ORD record
ord-3f2b7602ba694e89ab5a78f72d8d516e
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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