Water → HCID 86664930, compound

HRID 1256229Notes

Reaction equation

HRID 1256229 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]#[C:20][Si](C)(C)C)[CH:15]=[CH:14][C:13]=2[C:12]2=[N:25][N:26]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[C:27]([NH:28][CH:29]3[CH2:34][CH2:33][N:32]([S:35]([CH3:38])(=[O:37])=[O:36])[CH2:31][CH2:30]3)=[C:11]2[N:10]=1.O>C1COCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>[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]#[CH:20])[CH:15]=[CH:14][C:13]=2[C:12]2=[N:25][N:26]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:45])([CH3:44])[CH3:46])[C:27]([NH:28][CH:29]3[CH2:34][CH2:33][N:32]([S:35]([CH3:38])(=[O:37])=[O:36])[CH2:31][CH2:30]3)=[C:11]2[N:10]=1

Participants

5

Reactant 2

HCID 962WaterHCID 66770583HCID 66770583, compound

Product 1

HCID 86664930HCID 86664930, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 2724141Tetrabutylammonium FluorideSolvent

Procedure

A 30 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 74 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-2-{[2-(trimethylsilyl)ethoxy]methyl}-7-trimethylsilanylethynyl-2H-pyrazolo[4,3-c]isoquinoline in 5 ml of THF, 0.22 cm3 of tetrabutylammonium fluoride is added, and the mixture is stirred at RT for 30 min. It 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 mixture of DCM and AcOEt (85/15 by vol.), to give 47 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 (lemon yellow solid). MS (E/I): m/z=611 (M+).

Workup

  1. customA 30 ml round-bottomed flask equipped with a magnetic stirrer and with a septum
  2. additionis added
  3. extractionextracted with AcOEt
  4. washwashed with saturated NaCl solution
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under RP
  8. customThe product is purified by flash chromatography on silica gel (40-63 μm)
  9. washeluting with a mixture of DCM and AcOEt (85/15 by vol.)

Sources & evidence

ORD record
ord-0ab79a859e6c4015a51111017ada5905
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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