HCID 68283812, compound → HCID 68284543, compound

HRID 1469568Notes

Reaction equation

HRID 1469568 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-91e980c842574e76a9f1800ca6845b3c
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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