2-Chloromethyl 2-(trimethylsilyl)ethyl ether → HCID 66773858, compound

HRID 1256239Notes

Reaction equation

HRID 1256239 reaction equation
[Br:1][C:2]1[C:6]2[N:7]=[C:8]([C:15]3[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:16]=3[F:22])[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C:5]=2[NH:4][N:3]=1.[CH3:23][Si:24]([CH3:31])([CH3:30])[CH2:25][CH2:26][O:27][CH2:28]Cl>CN(C=O)C.C(N(CC)C(C)C)(C)C>[Br:1][C:2]1[C:6]2[N:7]=[C:8]([C:15]3[C:16]([F:22])=[CH:17][CH:18]=[CH:19][C:20]=3[F:21])[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C:5]=2[N:4]([CH2:28][O:27][CH2:26][CH2:25][Si:24]([CH3:31])([CH3:30])[CH3:23])[N:3]=1

Participants

5

Reactant 2

HCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178505720HCID 178505720, compound

Product 1

HCID 66773858HCID 66773858, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Procedure

A 50 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 890 mg of 3-bromo-5-(2,6-difluorophenyl)-1H-pyrazolo[4,3-c]isoquinoline in 20 ml of DMF, 2.46 ml of N,N-diisopropylethylamine and 658 μl of 2-(trimethylsilyl)ethoxymethyl chloride. After 16 h at RT, the mixture is poured into 50 ml of ice-water. The aqueous phase is extracted with 3 times 50 ml of AcOEt and the organic extracts are combined, washed with saturated NaCl solution, dried over MgSO4 and concentrated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with a mixture of cyclohexane and DCM (80/20 by vol.) then (50/50 by vol.), to give on one hand 498 mg of 3-bromo-5-(2,6-difluorophenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline, in the form of a white gum, LC-MS-DAD-ELSD: 492 (+)=(M+H)(+), and on the other hand 200 mg of 3-bromo-5-(2,6-difluorophenyl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinoline (white gum), LC-MS-DAD-ELSD: 492 (+)=(M+H)(+).

Workup

  1. customA 50 ml round-bottomed flask equipped with a magnetic stirrer and with a septum
  2. extractionThe aqueous phase is extracted with 3 times 50 ml of AcOEt
  3. washwashed with saturated NaCl solution
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under RP
  6. customThe product is purified by flash chromatography on silica gel (15-40 μm)
  7. washeluting with a mixture of cyclohexane and DCM (80/20 by vol.)

Sources & evidence

ORD record
ord-571db61901534a3eabc92c57c18a277d
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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