Water → HCID 66774046, compound

HRID 1256227Notes

Reaction equation

HRID 1256227 reaction equation
[Br:1][C:2]1[C:6]2[N:7]=[C:8]([C:16]3[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=3[F:23])[C:9]3[CH:10]=[C:11]([I:15])[CH:12]=[CH:13][C:14]=3[C:5]=2[NH:4][N:3]=1.C(N(C(C)C)CC)(C)C.[CH3:33][Si:34]([CH3:41])([CH3:40])[CH2:35][CH2:36][O:37][CH2:38]Cl.O>CN(C=O)C>[Br:1][C:2]1[C:6]2[N:7]=[C:8]([C:16]3[C:17]([F:23])=[CH:18][CH:19]=[CH:20][C:21]=3[F:22])[C:9]3[CH:10]=[C:11]([I:15])[CH:12]=[CH:13][C:14]=3[C:5]=2[N:4]([CH2:38][O:37][CH2:36][CH2:35][Si:34]([CH3:41])([CH3:40])[CH3:33])[N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178505721HCID 178505721, compound

Product 1

HCID 66774046HCID 66774046, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 150 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 1.2 g of 3-bromo-5-(2,6-difluorophenyl)-7-iodo-1H-pyrazolo[4,3-c]isoquinoline, prepared in step 1 of example 6, in 24 ml of DMF, 3 ml of diisopropylethylamine and 0.92 ml of 2-(trimethylsilyl)ethoxymethyl chloride. The mixture is stirred at RT for 24 h and then poured into water, extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. This gives 1.52 g of crude product, which is purified by chromatography on silica gel (20-45 μm), eluting with a DCM/methanol mixture (99.5/0.5 by vol.), to give on one hand 832 mg of 3-bromo-5-(2,6-difluorophenyl)-1-(2-trimethylsilanyl ethoxymethyl)-7-iodo-1H-pyrazolo[4,3-c]isoquinoline in the form of a white solid. MS (E/I): m/z=616 (M+), and on the other hand 526 mg of 3-bromo-5-(2,6-difluorophenyl)-2-(2-trimethylsilanyl-ethoxymethyl)-7-iodo-2H-pyrazolo[4,3-c]isoquinoline (ochre oil), which is used as it is in the following step. MS (E/I): m/z=616 (M+).

Workup

  1. customA 150 ml round-bottomed flask equipped with a magnetic stirrer and with a septum
  2. extractionextracted with AcOEt
  3. washwashed with saturated NaCl solution
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under RP
  7. customThis gives 1.52 g of crude product, which is purified by chromatography on silica gel (20-45 μm)
  8. washeluting with a DCM/methanol mixture (99.5/0.5 by vol.)

Sources & evidence

ORD record
ord-da8b65df2b7c4519814b36a1dd5e14b2
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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