Methyl iodide → 3-Carboxy-4-ethyl-9-isopropyl-9H-pyrido[3,4-b]indole

HRID 2217754Notes

Reaction equation

HRID 2217754 reaction equation
[CH2:1]([Li])[CH2:2]CC.[C:6]([C:9]1[N:24]=[CH:23][C:12]2[N:13]([CH:20]([CH3:22])[CH3:21])[C:14]3[C:19]([C:11]=2[CH:10]=1)=[CH:18][CH:17]=[CH:16][CH:15]=3)([OH:8])=[O:7].CC1(C)CCCC(C)(C)N1.CI>C1COCC1>[C:6]([C:9]1[N:24]=[CH:23][C:12]2[N:13]([CH:20]([CH3:21])[CH3:22])[C:14]3[C:19]([C:11]=2[C:10]=1[CH2:1][CH3:2])=[CH:18][CH:17]=[CH:16][CH:15]=3)([OH:8])=[O:7]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 130352,2,6,6-TetramethylpiperidineHCID 69309518HCID 69309518, compoundHCID 178418339Butyllithium

Product 1

HCID 693095113-Carboxy-4-ethyl-9-isopropyl-9H-pyrido[3,4-b]indoleYield 33.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

n-Butyllithium (2.5 M in hexanes, 3.2 ml, 8 mmol) and 3-carboxy-9-isopropyl-9H-pyrido[3,4-b]indole (Method 2; 504 mg, 2 mmol) were added to a solution of 2,2,6,6-tetramethyl piperidine (1.01 ml, 6 mmol) in THF (15 ml) at −50° C. The mixture was allowed to stir for 30 minutes warming to 0° C. Methyl iodide (0.15 ml, 2.4 mmol) was then added in a single portion and the mixture was left at 0° C. for a further 30 minutes and at room temperature for a further 16 hours. The mixture was concentrated in vacuo and the residue was dissolved in DCM. The solution was washed with 1 M HCl and then with water. The organic phase was separated, dried and concentrated in vacuo. The crude product was purified by preparative HPLC eluting over a gradient of 20-90% MeCN in water (0.1% TFA). The product was obtained as a yellow solid (190 mg) after evaporation of the appropriate fractions. NMR (300 MHz) 9.16 (s, 1H), 8.39 (d, 1H), 8.01 (d, 1H), 7.72 (t, 1H), 7.43 (t, 1H), 5.39 (m, 1H), 3.60 (q, 2H), 1.67 (d, 6H), 1.38 (t, 3H).

Workup

  1. waitthe mixture was left at 0° C. for a further 30 minutes and at room temperature for a further 16 hours
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionthe residue was dissolved in DCM
  4. washThe solution was washed with 1 M HCl
  5. customThe organic phase was separated
  6. customdried
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by preparative HPLC
  9. washeluting over a gradient of 20-90% MeCN in water (0.1% TFA)

Sources & evidence

ORD record
ord-95f01382314b4606ad88ed713f55a089
Source dataset
uspto-grants-2008_08
Patent number
US07408064B2

Reaction notes

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