Trifluoroacetic acid → HCID 49764268, compound

HRID 1256241Notes

Reaction equation

HRID 1256241 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]([CH:34]4[CH2:36][CH2:35]4)(=[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]([CH:34]4[CH2:35][CH2:36]4)(=[O:32])=[O:33])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67494599HCID 67494599, compound

Product 1

HCID 49764268HCID 49764268, compoundYield 35.3%

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 57 mg of 5-(2,6-difluorophenyl)-3-{[1-(cyclopropylsulphonyl)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, 0.3 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, 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 cyclohexane and AcOEt (80/20 by vol.), to give 16 mg of 5-(2,6-difluorophenyl)-3-{[1-(cyclopropylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile (yellow solid). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.89-1.04 (m, 4 H) 1.67 (m, 2 H) 2.10 (m, 2 H) 2.58 (m, 1 H) 3.00 (m, 2 H) 3.62 (m, 2 H) 3.82 (m, 1 H) 6.21 (d, J=7.8 Hz, 1 H) 7.34 (t, J=7.8 Hz, 2 H) 7.70 (m, 1 H), 8.19 (broad s, 1 H) 8.27 (dd, J=8.5, 1.5 Hz, 1 H) 8.56 (d, J=8.5 Hz, 1 H) 13.07 (s, 1 H) LC-MS-DAD-ELSD: 509 (+)=(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 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 cyclohexane and AcOEt (80/20 by vol.)

Sources & evidence

ORD record
ord-40e6dc18710a488cbe27a20067132571
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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