Dimethylformamide → 3-bromo-5-(2,6-difluorophenyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-7-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-4-yl)-2H-pyrazolo[4,3-c]isoquinoline

HRID 1256254Notes

Reaction equation

HRID 1256254 reaction equation
[Br:1][C:2]1[N:3]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[N:4]=[C:5]2[C:14]3[CH:13]=[CH:12][C:11]([C:15]4[CH:16]=[N:17][NH:18][CH:19]=4)=[CH:10][C:9]=3[C:8]([C:20]3[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=3[F:27])=[N:7][C:6]=12.CN(C=O)C.C(N(C(C)C)CC)(C)C.[CH3:50][Si:51]([CH3:58])([CH3:57])[CH2:52][CH2:53][O:54][CH2:55]Cl>O>[Br:1][C:2]1[N:3]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[N:4]=[C:5]2[C:14]3[CH:13]=[CH:12][C:11]([C:15]4[CH:16]=[N:17][N:18]([CH2:55][O:54][CH2:53][CH2:52][Si:51]([CH3:58])([CH3:57])[CH3:50])[CH:19]=4)=[CH:10][C:9]=3[C:8]([C:20]3[C:21]([F:27])=[CH:22][CH:23]=[CH:24][C:25]=3[F:26])=[N:7][C:6]=12

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 667722013-bromo-5-(2,6-difluorophenyl)-7-(1H-pyrazol-4-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinoline

Product 1

HCID 667720733-bromo-5-(2,6-difluorophenyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-7-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-4-yl)-2H-pyrazolo[4,3-c]isoquinoline

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

115 mg of 3-bromo-5-(2,6-difluorophenyl)-7-(1H-pyrazol-4-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinoline are introduced into 2 ml of DMF, 0.26 ml of diisopropylethylamine and 77 μl of 2-(trimethylsilyl)ethoxymethyl chloride. The reaction mixture is stirred at RT for 18 h and then poured into water, extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. The product is purified by chromatography on silica gel (20-45 μm), eluting with a mixture of DCM and methanol (98/02 by vol.), to give 116 mg of 3-bromo-5-(2,6-difluorophenyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-7-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazol-4-yl)-2H-pyrazolo[4,3-c]isoquinoline (yellow powder). 1H NMR: −0.01 (d, J=5.9 Hz, 4 H) 0.82-1.00 (m, 1 H) 3.60 (t, J=7.8 Hz, 1 H) 3.77 (t, 1 H) 5.46 (s, 1 H) 5.92 (s, 1 H) 7.42 (t, 1 H) 7.71-7.83 (m, 1 H) 8.03 (s, 1 H) 8.28 (dd, 1 H) 8.43 (s, 1 H) 8.58 (d, J=8.3 Hz, 1 H).

Workup

  1. extractionextracted with AcOEt
  2. washwashed with saturated NaCl solution
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under RP
  6. customThe product is purified by chromatography on silica gel (20-45 μm)
  7. washeluting with a mixture of DCM and methanol (98/02 by vol.)

Sources & evidence

ORD record
ord-0ab19500ba944c74b37d3e76dc5423af
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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