HCID 68283812, compound → HCID 68284543, compound

HRID 2408733Notes

Reaction equation

HRID 2408733 reaction equation
CO[C:3](=[O:28])[CH2:4][CH:5]([C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)[CH2:6][N:7]1[C:15]2[CH:14]=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=2[C:9]2[CH2:17][N:18]([CH3:21])[CH2:19][CH2:20][C:8]1=2.[C:29]([Li])([CH3:32])([CH3:31])[CH3:30]>C1COCC1>[CH3:21][N:18]1[CH2:19][CH2:20][C:8]2[N:7]([CH2:6][CH:5]([C:22]3[CH:23]=[CH:24][N:25]=[CH:26][CH:27]=3)[CH2:4][C:3](=[O:28])[C:29]([CH3:32])([CH3:31])[CH3:30])[C:15]3[CH:14]=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=3[C:9]=2[CH2:17]1

Participants

4

Reactant 2

HCID 68283812HCID 68283812, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 68284543HCID 68284543, compoundYield 108%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

4-(2,8-Dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-3-pyridin-4-yl-butyricacidmethylester (1.5 g, 3.9 mmol) was dissolved in THF (50 mL) and cooled to −78° C., tert-butyl lithium (16% in pentane) (6 mL, 15.13 mmol) was added dropwise under nitrogen. The reaction mixture was stirred at −78° C. for 90 min. After complete consumption of starting material, the reaction mixture was quenched with ammonium chloride solution and the reaction mixture was allowed to come to RT and extracted with EtOAc (3×100 mL). The combined organic layer was dried over anhydrous sodium sulfate and concentrated to obtain 1.7 g of crude 6-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2,2-dimethyl-5-pyridin-4-yl-hexan-3-one. 1H NMR (CDCl3, freebase) δ (ppm): 8.41 (d, 2H), 7.31 (d, 1H), 7.19 (s, 1H), 7.1 (d, 1H), 6.93 (d, 2H), 4.25 (dd, 1H), 3.9 (t, 2H), 3.8 (m, 1H), 3.67 (dd, 1H), 2.87 (m, 3H), 2.71 (m, 2H), 2.51 (s, 3H), 2.42 (s, 3H), 2.1 (m, 1H), 1.21 s (9H). Separation by chiral HPLC provides enantiomers II-222a-b.

Workup

  1. customAfter complete consumption of starting material
  2. customthe reaction mixture was quenched with ammonium chloride solution
  3. customto come to RT
  4. extractionextracted with EtOAc (3×100 mL)
  5. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9e73fcdd74524e6e86889eefd27887cc
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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