HCID 68283527, compound → HCID 68283997, compound

HRID 2408681Notes

Reaction equation

HRID 2408681 reaction equation
C([N:4]1[CH2:27][CH2:26][C:7]2[N:8]([CH:16]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([CH3:25])=[CH:23][CH:24]=3)[CH3:18])[C:9]3[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][C:14]=3[C:6]=2[CH2:5]1)C=C>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:15][C:12]1[CH:11]=[CH:10][C:9]2[N:8]([CH:16]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([CH3:25])=[CH:23][CH:24]=3)[CH3:18])[C:7]3[CH2:26][CH2:27][NH:4][CH2:5][C:6]=3[C:14]=2[CH:13]=1

Participants

4

Reactant 1

HCID 68283527HCID 68283527, compound

Product 1

HCID 68283997HCID 68283997, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a de-aerated solution of 2-allyl-8-methyl-5-[2-(6-methyl-pyridin-3-yl)-propenyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (750 mg, 2.1 mmol) in DCM (7.5 mL) were added 1,3-dimethylbarbutaric acid (984 mg, 6.302 mmol) and Pd(PPh3)4 (48 mg, 0.042 mmol), and the reaction mixture stirred for 1 h at RT. The reaction mixture was concentrated and the residue diluted with 25% saturated potassium carbonate and extracted with EtOAc (3×30 mL). The combined organic layer was washed with water (2×25 mL), dried over anhydrous sodium sulfate and concentrated to afford crude material, which was purified by column chromatography using neutral alumina and 2% MeOH-DCM followed by reverse phase HPLC to yield 8-methyl-5-[2-(6-methyl-pyridin-3-yl)-propenyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (180 mg). 1H NMR (CD3OD, TFA salt) δ (ppm): 8.92 (s, 1H), 8.65 (d, 1H), 7.90 (d, 1H), 7.36 (d, 2H), 7.18 (d, 1H), 7.16 (d, 1H), 4.50 (s, 2H), 3.65 (t, 2H), 3.10 (t, 2H), 2.80 (s, 3H), 2.42 (s, 3H), 2.05 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue diluted with 25% saturated potassium carbonate
  3. extractionextracted with EtOAc (3×30 mL)
  4. washThe combined organic layer was washed with water (2×25 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customto afford crude material, which
  8. customwas purified by column chromatography

Sources & evidence

ORD record
ord-8206ee754aad4acebb11ac58995aa132
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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