Dimethylbarbituric acid → HCID 60197782, compound

HRID 1469426Notes

Reaction equation

HRID 1469426 reaction equation
C([N:4]1[CH2:26][CH2:25][C:7]2[N:8]([CH2:16][CH:17]([C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)[OH: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.CN1C(=O)CC(=O)N(C)C1=O>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]([CH2:16][CH:17]([C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)[OH:18])[C:7]3[CH2:25][CH2:26][NH:4][CH2:5][C:6]=3[C:14]=2[CH:13]=1

Participants

5

Reactant 2

HCID 69860Dimethylbarbituric acidHCID 68283510HCID 68283510, compound

Product 1

HCID 60197782HCID 60197782, compoundYield 5.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

2-(2-Allyl-8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-3-yl-ethanol (1.0 g, 2.8 mmol) was dissolved in DCM and the solution was purged with nitrogen for 5 min. 1,3-Dimethylbarbituric acid (1.34 g, 8.6 mmol) and Pd(PPh3)4 (66.5 mg, 0.056 mmol) were added and the reaction mixture was stirred at RT for 3 h. The reaction mixture was concentrated under reduced pressure, and the residue was basified with saturated aqueous potassium carbonate, and extracted with EtOAc (3×50 mL). The combined organic layer was washed with saturated aqueous potassium carbonate (6×20 mL), dried over anhydrous sodium sulfate and concentrated. The crude product was purified by reverse phase chromatography to obtain 50 mg of 2-(8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-3-yl-ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 8.47 (s, 1H), 8.41 (d, 1H), 7.59 (d, 1H), 7.19 (m, 3H), 7.10 (s, 1H), 7.00 (d, 1H), 5.0 (t, 1H), 4.10 q (d, 2H), 3.92 q (d, 2H), 3.10 (m, 2H), 2.90 (m, 2H), 2.47 (m, 1H), 2.42 (s, 3H). This racemate was separated by chiral semi-preparative HPLC to obtain enantiomers 9a and 9b.

Workup

  1. customthe solution was purged with nitrogen for 5 min
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined organic layer was washed with saturated aqueous potassium carbonate (6×20 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe crude product was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-0af3cbfe24bf4f6bb2125318574abe7d
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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