Hexane → 6-((S)-2-(((2S,5R)-3,6-diethoxy-5-isopropyl-2,5-dihydropyrazin-2-yl)methyl)-3-methylbutyl)-1-(3-methoxypropyl)-1H-indazole

HRID 660372Notes

Reaction equation

HRID 660372 reaction equation
[CH2:1]([O:3][C:4]1[C@@H:5]([CH:13]([CH3:15])[CH3:14])[N:6]=[C:7]([O:10][CH2:11][CH3:12])[CH2:8][N:9]=1)[CH3:2].[Li]CCCC.CCCCCC.Br[CH2:28][C@@H:29]([CH:45]([CH3:47])[CH3:46])[CH2:30][C:31]1[CH:39]=[C:38]2[C:34]([CH:35]=[N:36][N:37]2[CH2:40][CH2:41][CH2:42][O:43][CH3:44])=[CH:33][CH:32]=1>C1COCC1>[CH2:11]([O:10][C:7]1[C@H:8]([CH2:28][C@@H:29]([CH:45]([CH3:47])[CH3:46])[CH2:30][C:31]2[CH:39]=[C:38]3[C:34]([CH:35]=[N:36][N:37]3[CH2:40][CH2:41][CH2:42][O:43][CH3:44])=[CH:33][CH:32]=2)[N:9]=[C:4]([O:3][CH2:1][CH3:2])[C@@H:5]([CH:13]([CH3:15])[CH3:14])[N:6]=1)[CH3:12]

Participants

6

Reactant 4

HCID 8058HexaneHCID 5325957(2R)-3,6-diethoxy-2-(propan-2-yl)-2,5-dihydropyrazineHCID 68783219(R)-6-(2-(bromomethyl)-3-methylbutyl)-1-(3-methoxypropyl)-1H-indazoleHCID 178418339Butyllithium

Product 1

HCID 687852626-((S)-2-(((2S,5R)-3,6-diethoxy-5-isopropyl-2,5-dihydropyrazin-2-yl)methyl)-3-methylbutyl)-1-(3-methoxypropyl)-1H-indazoleYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of (R)-3,6-diethoxy-2-isopropyl-2,5-dihydropyrazine (480 mg, 2.3 mmol) in anhydrous THF (7 mL) at −78° C. was added dropwise 2.5 M n-BuLi in hexane (0.9 mL, 2.3 mmol). After stirring for 2 h at −78° C., a solution of (R)-6-(2-(bromomethyl)-3-methylbutyl)-1-(3-methoxypropyl)-1H-indazole (530 mg, 1.5 mmol) in THF (2 mL) was added dropwise. The mixture was stirred for 1 h at −78° C., then warmed to rt and stirred for 12 h. The reaction mixture was quenched with satd aq NH4Cl and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine, dried over Na2SO4, evaporated, and purified by flash chromatography on silica gel to give 6-((S)-2-(((2S,5R)-3,6-diethoxy-5-isopropyl-2,5-dihydropyrazin-2-yl)methyl)-3-methylbutyl)-1-(3-methoxypropyl)-1H-indazole (493 mg, 68%). MS: 485 (M++1).

Workup

  1. stirringThe mixture was stirred for 1 h at −78° C.
  2. temperaturewarmed to rt
  3. stirringstirred for 12 h
  4. customThe reaction mixture was quenched with satd aq NH4Cl
  5. extractionextracted with EtOAc (3×10 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. custompurified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-aae48348d84745e19ab32e46571e7d47
Source dataset
uspto-grants-2011_12
Patent number
US08084485B2

Reaction notes

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