Methanol → HCID 66770599, compound

HRID 1256256Notes

Reaction equation

HRID 1256256 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]#[CH:20])[CH:15]=[CH:14][C:13]=2[C:12]2=[N:21][N:22]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[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.CO.CN(C=O)C.C[Si]([N:54]=[N+:55]=[N-:56])(C)C>[Cu]I.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]3[CH:20]=[N:56][NH:55][N:54]=3)[CH:15]=[CH:14][C:13]=2[C:12]2=[N:21][N:22]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:40])([CH3:42])[CH3:41])[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

Participants

7

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 78378Azidotrimethylsilane2×HCID 86664930HCID 86664930, compound

Product 1

HCID 66770599HCID 66770599, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

239 mg of 5-(2,6-difluorophenyl)-3-([1-(methylsulphonyl)piperidin-4-yl]amino}-2-{[2-(trimethylsilyl)ethoxy]methyl}-7-ethynyl-2H-pyrazolo[4,3-c]isoquinoline, prepared in step 4 of example 7, are introduced into 4 ml of methanol and 4 ml of DMF, and 208 μL of trimethylsilyl azide and 15 mg of copper(I) iodide are added. After 2 h of heating at 100° C., 104 μl of trimethylsilyl azide and 7 mg of copper(I) iodide are added and heating at 100° C. is continued for 2 h. After cooling, the mixture is poured into water, extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (40-63 μm), eluting with a DCM/methanol mixture (95/05 by vol.), to give 121 mg of 5-(2,6-difluorophenyl)-N-[1-(methylsulphonyl)piperidin-4-yl]-7-(2H-1,2,3-triazol-4-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinolin-3-amine (yellow foam). 1H NMR: −0.04 (s, 9 H) 0.90 (m, 2 H) 1.61 (m, 2 H) 2.12 (m, 2 H) 275 (m, 2 H) 2.85 (s, 3 H) 3.57 (m, 2 H) 3.68 (m, 2 H) 4.47 (m, 1 H) 5.66 (s, 2 H) 6.49 (d, J=8.4 Hz, 1 H) 7.36 (t, J=8.0 Hz, 2 H) 7.67 (m, 1 H) 8.01 (broad s, 1 H) 8.25 (broad d, J=8.5 Hz, 1 H) 8.41 (d, J=8.5 Hz, 1 H) 8.43 (partially masked broad m, 1 H) 15.28 (broad m, 1 H).

Workup

  1. additionare added
  2. temperatureheating at 100° C.
  3. temperatureAfter cooling
  4. extractionextracted with AcOEt
  5. washwashed with saturated NaCl solution
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under RP
  9. customThe product is purified by flash chromatography on silica gel (40-63 μm)
  10. washeluting with a DCM/methanol mixture (95/05 by vol.)

Sources & evidence

ORD record
ord-57a708dd73624223a18b4e469490efa7
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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