Water → 1-benzyl-3-(tetrahydro-pyran-4-ylmethyl)-4-(1-triisopropylsilanyl-1H-indazol-5-yl)-piperazin-2-one

HRID 1672154Notes

Reaction equation

HRID 1672154 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=2)[N:19]([Si:23]([CH:30]([CH3:32])[CH3:31])([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25])[N:18]=[CH:17]3)[CH2:10][C:9]1=[O:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])(CC)C.Br[CH2:40][CH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1.O>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=2)[N:19]([Si:23]([CH:27]([CH3:29])[CH3:28])([CH:30]([CH3:32])[CH3:31])[CH:24]([CH3:25])[CH3:26])[N:18]=[CH:17]3)[CH:10]([CH2:40][CH:41]2[CH2:46][CH2:45][O:44][CH2:43][CH2:42]2)[C:9]1=[O:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 27732864-(Bromomethyl)oxaneHCID 673353951-benzyl-4-(1-triisopropylsilanyl-1H-indazol-5-yl)-piperazin-2-oneHCID 178418400CID 53628100

Product 1

HCID 673367111-benzyl-3-(tetrahydro-pyran-4-ylmethyl)-4-(1-triisopropylsilanyl-1H-indazol-5-yl)-piperazin-2-oneYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-benzyl-4-(1-triisopropylsilanyl-1H-indazol-5-yl)-piperazin-2-one (0.78 g, 1.7 mmol) in 8.5 mL THF at −78° C. was added sec-butyllitium (1.3 mL, 1.9 mmol) drop-wise over 5 minutes. After 30 minutes 4-bromomethyl-tetrahydropyran (0.36 g, 2.0 mmol) was added in one portion and mixture was warmed to room temperature. After 18 hours H2O was added and the mixture was extracted with ethyl acetate. The combined organic layerss were washed with H2O, brine, dried over NaSO4, filtered and concentrated in vacuo. Purification via flash chromatography afforded 1-benzyl-3-(tetrahydro-pyran-4-ylmethyl)-4-(1-triisopropylsilanyl-1H-indazol-5-yl)-piperazin-2-one (0.55g, 90%) as a white foam.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe combined organic layerss were washed with H2O, brine
  3. dry with materialdried over NaSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification via flash chromatography

Sources & evidence

ORD record
ord-a34d32927d4145dcb8fb7e93531423d7
Source dataset
uspto-grants-2011_08
Patent number
US07998963B2

Reaction notes

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