Trifluoroacetic acid → HCID 49764144, compound

HRID 1256240Notes

Reaction equation

HRID 1256240 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]=[CH:16][CH:15]=[CH:14][C:13]=2[C:12]2[N:19](COCC[Si](C)(C)C)[N:20]=[C:21]([NH:22][CH:23]3[CH2:28][CH2:27][N:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:25][CH2:24]3)[C:11]=2[N:10]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.O>[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]=[CH:16][CH:15]=[CH:14][C:13]=2[C:12]2[NH:19][N:20]=[C:21]([NH:22][CH:23]3[CH2:24][CH2:25][N:26]([S:29]([CH3:32])(=[O:30])=[O:31])[CH2:27][CH2:28]3)[C:11]=2[N:10]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67494325HCID 67494325, compound

Product 1

HCID 49764144HCID 49764144, compoundYield 16.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 10 ml round-bottomed flask is charged with 71 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline in 3 ml of DCM. After cooling to 0° C. using an ice bath, 0.3 ml of TFA is added and the reaction mixture is stirred at RT for 16 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 with a mixture of DCM and methanol (95/5 by vol.), to give 9 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline (beige solid). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.67 (m, 2 H) 2.11 (m, 2 H) 2.88 (s, 3 H) 2.90 (m, 2 H) 3.56 (m, 2 H) 3.79 (broad s, 1 H) 6.04 (broad m, 1 H) 7.32 (m, 2 H) 7.52-7.74 (m, 3 H) 7.92 (m, 1 H) 8.40 (d, 1 H) 12.76 (broad s, 1 H); LC-MS-DAD-ELSD: 458 (+)=(M+H)(+).

Workup

  1. concentrationIt is concentrated under RP
  2. customthe solid obtained
  3. extractionextracted with three times 20 ml of AcOEt
  4. dry with materialThe organic phase is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under RP
  7. customThe product is purified by flash chromatography on silica gel (15-40 μm)
  8. washeluting with DCM and with a mixture of DCM and methanol (95/5 by vol.)

Sources & evidence

ORD record
ord-0e572fc638d243b2a7ce0feeef12e13c
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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