Trifluoroacetic acid → HCID 49764270, compound

HRID 1256243Notes

Reaction equation

HRID 1256243 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]#[N:20])[CH:15]=[CH:14][C:13]=2[C:12]2[N:21](COCC[Si](C)(C)C)[N:22]=[C:23]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([S:31]([CH2:34][CH3:35])(=[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>[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]#[N: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]([CH2:34][CH3:35])(=[O:32])=[O:33])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66774622HCID 66774622, compound

Product 1

HCID 49764270HCID 49764270, compoundYield 68.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 10 ml round-bottomed flask equipped with a magnetic stirrer is charged with 50 mg of 5-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1-([2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile in 5 ml of DCM. After cooling to 0° C. using an ice bath, 0.1 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 20 ml of water and extracted with three times 20 ml of AcOEt. The combined organic phases are 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 with a mixture of DCM and methanol (90/10 by vol.), to give 27 mg of 5-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile (yellow solid). 1H NMR (400 MHz, DMSO-d6) 1.23 (t, J=7.3 Hz, 3 H) 1.63 (m, 2 H) 2.09 (m, 2 H) 2.97 (m, 2 H) 3.05 (q, J=7.3 Hz, 2 H) 3.61 (m, 2 H) 3.81 (m, 1 H) 6.23 (broad m, 1 H) 7.34 (t, J=7.8 Hz, 2 H) 7.70 (m, 1 H) 8.18 (broad s, 1 H) 8.27 (broad d, J=8.5 Hz, 1 H) 8.56 (d, J=8.5 Hz, 1 H) 13.07 (broad s, 1 H) LC-MS-DAD-ELSD: 497 (+)=(M+H)(+).

Workup

  1. customA 10 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 combined organic phases are 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 and with a mixture of DCM and methanol (90/10 by vol.)

Sources & evidence

ORD record
ord-2796231dfb68426eb358bb299e88e10d
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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