Dimethylbarbituric acid → HCID 68283473, compound

HRID 2408591Notes

Reaction equation

HRID 2408591 reaction equation
C([N:4]1[CH2:26][CH2:25][C:7]2[N:8]([CH2:16][CH:17]([C:19]3[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=3)[OH:18])[C:9]3[CH:10]=[CH:11][C:12]([Cl: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>[Cl:15][C:12]1[CH:11]=[CH:10][C:9]2[N:8]([CH2:16][CH:17]([C:19]3[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=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 60197483HCID 60197483, compound

Product 1

HCID 68283473HCID 68283473, compoundYield 61.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

2-(2-Allyl-8-chloro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethanol (4.0 g, 10.87 mmol) was dissolved in DCM (350 mL) and nitrogen was purged for 10 min into the reaction mixture. 1,3-Dimethyl barbituric acid (5.08 g, 32.62 mmol) and Pd(PPh3)4 (251 mg, 0.217 mmol) was added and stirred for 2 h at RT. After consumption of starting material, the reaction mixture was diluted with saturated potassium carbonate (200 mL) and extracted with DCM (2×100 mL). The combined organic layer was dried over anhydrous sodium sulfate and concentrated, and the crude mixture crystallized in MeOH (5 mL) and ether (50 mL) to obtain 2.2 g of 2-(8-chloro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 8.58 (d, 2H), 7.37 (s, 1H), 7.25 (d, 2H), 7.23 (d, 1H), 7.13 (d, 1H), 5.0 (t, 1H), 4.15 (d, 2H), 3.99 (s, 2H), 3.19 (m, 2H), 2.81 (m, 1H), 2.53 (m, 1H). Separation by chiral HPLC provided enantiomers 10a and 10b. Optical rotations: Compound No. 10a, (−) 34.60 (c 0.55, Chloroform, 99.16% HPLC purity); Compound No. 10b, (+) 31.78 (c 0.53, Chloroform, 92.71% HPLC purity).

Workup

  1. customnitrogen was purged for 10 min into the reaction mixture
  2. customAfter consumption of starting material
  3. additionthe reaction mixture was diluted with saturated potassium carbonate (200 mL)
  4. extractionextracted with DCM (2×100 mL)
  5. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customthe crude mixture crystallized in MeOH (5 mL)

Sources & evidence

ORD record
ord-196db1a33fa541afb809fb1afa71aea3
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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