Ammonia → HCID 49764394, compound

HRID 1256247Notes

Reaction equation

HRID 1256247 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.S(=O)(=O)(O)[OH:45].N>C1(C)C=CC=CC=1>[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]([NH2:20])=[O:45])[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 3

HCID 222AmmoniaHCID 1118Sulfuric AcidHCID 66774622HCID 66774622, compound

Product 1

HCID 49764394HCID 49764394, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

A 100 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 396 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 4 ml of toluene. After cooling to 0° C. using an ice bath, 0.64 ml of 95% sulphuric acid is added and the mixture is stirred at RT for 15 h. It is cooled to 0° C. and neutralized with 9 ml of 7.5M aqueous NH3 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 MeOH (95/05 by vol.). This gives 174 mg of 5-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxamide (yellow solid). MS (E/I): m/z=514 (M+); 1H NMR: 1.23 (t, J=7.4 Hz, 3H); 1.65 (m, 2H); 2.09 (m, 2H); 2.98 (m, 2H); 3.05 (q, J=7.4 Hz, 2H); 3.62 (m, 2H); 3.81 (m, 1H); 6.09 (d, J=8.3 Hz, 1H); 7.33 (m, 2H); 7.55 (broad s, 1H); 7.68 (m, 1H); 8.17 (broad s, 1H); 8.23 (broad s, 1H); 8.35 (broad d, J=8.8 Hz, 1H); 8.45 (d, J=8.8 Hz, 1H); 12.85 (s, 1H).

Workup

  1. customA 100 ml round-bottomed flask equipped with a magnetic stirrer and with a septum
  2. extractionThe product is extracted with AcOEt
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under RP
  6. customIt is purified by flash chromatography on silica gel (15-40 μm)
  7. washeluting with a mixture of DCM and MeOH (95/05 by vol.)

Sources & evidence

ORD record
ord-73c2dbb5371d494e969c45b1bb63d3b1
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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