Trifluoroacetic acid → HCID 49764140, compound

HRID 1256226Notes

Reaction equation

HRID 1256226 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]([F:19])[CH:15]=[CH:14][C:13]=2[C:12]2[N:20](COCC[Si](C)(C)C)[N:21]=[C:22]([NH:23][CH:24]3[CH2:29][CH2:28][N:27]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:26][CH2:25]3)[C:11]=2[N:10]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.O.N>[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]([F:19])[CH:15]=[CH:14][C:13]=2[C:12]2[NH:20][N:21]=[C:22]([NH:23][CH:24]3[CH2:29][CH2:28][N:27]([S:30]([CH3:33])(=[O:31])=[O:32])[CH2:26][CH2:25]3)[C:11]=2[N:10]=1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66774730HCID 66774730, compound

Product 1

HCID 49764140HCID 49764140, compoundYield 8%

Reagents, catalysts & solvents 3

HCID 222AmmoniaSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A round-bottomed flask equipped with a septum having a top-mounted argon intake is charged with 95 mg of 5-(2,6-difluorophenyl)-7-fluoro-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}1-([2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline in 10 ml of DCM. After cooling to 0° C. using an ice bath, 0.173 ml of TFA are added and the mixture is stirred at RT for 20 h. It is concentrated under RP and the solid obtained is taken up in 30 ml of water and 2 ml of 0.75M aqueous ammonia solution. The product is extracted with AcOEt, dried over MgSO4, filtered and concentrated under RP. It is purified by flash chromatography on silica gel (15-40 μm), eluting with a mixture of DCM and methanol (95/05 by vol.), to give 6 mg of 5-(2,6-difluorophenyl)-7-fluoro-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline (yellow solid). MS (E/I): m/z=475 (M+); 1H NMR: 1.67 (m, 2 H) 2.10 (m, 2 H) 2.87 (s, 3 H) 2.90 (m, 2 H) 3.56 (m, 2 H) 3.79 (m, 1H) 6.08 (d, J=8.3 Hz, 1 H) 7.29 (m, 1 H) 7.33 (t, J=7.8 Hz, 2 H) 7.68 (m, 1 H) 7.88 (broad t, J=9.3 Hz, 1 H) 8.50 (dd, J=9.3, 5.4 Hz, 1 H) 12.80 (s, 1 H)*.

Workup

  1. customA round-bottomed flask equipped with a septum
  2. concentrationIt is concentrated under RP
  3. customthe solid obtained
  4. extractionThe product is extracted with AcOEt
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under RP
  8. customIt is purified by flash chromatography on silica gel (15-40 μm)
  9. washeluting with a mixture of DCM and methanol (95/05 by vol.)

Sources & evidence

ORD record
ord-6c9f9eae90e2454d962eb1f69526ddc5
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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