Ammonia → HCID 49764011, compound

HRID 1256220Notes

Reaction equation

HRID 1256220 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]([CH2:19][OH: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]([CH3:34])(=[O:33])=[O:32])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1.C(O)(C(F)(F)F)=O.N>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]([CH2:19][OH: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]([CH3:34])(=[O:32])=[O:33])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 6422Trifluoroacetic acidHCID 66771726HCID 66771726, compound

Product 1

HCID 49764011HCID 49764011, compoundYield 35.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 30 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 46 mg of [5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinolin-7-yl]methanol in 4 ml of DCM. After cooling to 0° C. using an ice bath, 0.45 ml of TFA are added and the mixture is stirred at RT for 2 h. It is concentrated under RP and the solid obtained is taken up in 25 ml of water and 0.75 ml of a 0.75M aqueous ammonia solution. It is extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. Chromatography on silica gel (20-45 μm), eluting with a mixture of DCM and methanol (92.5/7.5 by vol.), gives 13 mg of [5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinolin-7-yl]methanol (yellow solid). MS (E/I): m/z=487 (M+); 1H NMR: 1.67 (m, 2H); 2.11 (m, 2H); 2.87 (s, 3H); 2.90 (m, 2H); 3.56 (m, 2H); 3.79 (m, 1H); 4.63 (d,. J=57 Hz, 2H); 5.34 (t, J=5.7 Hz, 1H); 5.98 (d, J=7.8 Hz, 1H); 7.31 (m, 2H); 7.59 (broad s, 1H); 7.66 (m, 1H); 7.83 (broad d, J=8.3 Hz, 1H); 8.35 (d, J=8.3, 1H); 12.68 (s, 1H).

Workup

  1. customA 30 ml round-bottomed flask equipped with a magnetic stirrer and with a septum
  2. concentrationIt is concentrated under RP
  3. customthe solid obtained
  4. extractionIt is extracted with AcOEt
  5. washwashed with saturated NaCl solution
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under RP
  9. washChromatography on silica gel (20-45 μm), eluting with a mixture of DCM and methanol (92.5/7.5 by vol.)

Sources & evidence

ORD record
ord-8988529cc18d4a3b8d19257c606e7233
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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