Dimethylbarbituric acid → HCID 60196973, compound

HRID 2408592Notes

Reaction equation

HRID 2408592 reaction equation
C([N:4]1[CH2:16][CH2:15][C:14]2[N:13]([CH2:17][C:18]([C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)([OH:20])[CH3:19])[C:12]3[N:11]=[CH:10][C:9]([Cl:27])=[CH:8][C:7]=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:27][C:9]1[CH:10]=[N:11][C:12]2[N:13]([CH2:17][C:18]([C:21]3[CH:22]=[CH:23][N:24]=[CH:25][CH:26]=3)([OH:20])[CH3:19])[C:14]3[CH2:15][CH2:16][NH:4][CH2:5][C:6]=3[C:7]=2[CH:8]=1

Participants

5

Reactant 2

HCID 69860Dimethylbarbituric acidHCID 68284186HCID 68284186, compound

Product 1

HCID 60196973HCID 60196973, compoundYield 42.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

1-(6-Allyl-3-chloro-5,6,7,8-tetrahydro-1,6,9-triaza-fluoren-9-yl)-2-pyridin-4-yl-propan-2-ol (260 mg, 0.680 mmol) was dissolved in DCM (7 mL) and N2 was purged into the reaction mixture. 1,3-Dimethyl barbituric acid (318 mg, 2.04 mmol) and Pd(PPh3)4 (15 mg, 0.013 mmol) was added and the mixture stirred for 45 min at RT. After consumption of starting material, the reaction mixture was diluted with saturated potassium carbonate and extracted with DCM (3×50 mL). The combined organic layer was dried over anhydrous sodium sulfate and concentrated, and the crude product was purified by reverse phase chromatography to obtain 100 mg of 1-(3-chloro-5,6,7,8-tetrahydro-1,6,9-triaza-fluoren-9-yl)-2-pyridin-4-yl-propan-2-ol. 1H NMR (CDCl3, freebase) δ (ppm): 8.51 (d, 2H), 8.14 (s, 1H), 7.67 (s, 1H), 7.33 (d, 2H), 4.39 (d, 1H), 4.36 (d, 1H), 3.93 q (d, 2H), 3.16 (m, 2H), 2.62 (m, 1H), 2.40 (m, 1H), 1.57 (s, 3H). Separation by chiral HPLC provided enantiomers 12a and 12b. Optical rotations: Compound No. 12a, (+) 121.78 (c 0.53, Chloroform, 97.32% HPLC purity); Compound No. 12b, (−) 118.34 (c 0.54, Chloroform, 99.01% HPLC purity).

Workup

  1. customN2 was purged into the reaction mixture
  2. customAfter consumption of starting material
  3. additionthe reaction mixture was diluted with saturated potassium carbonate
  4. extractionextracted with DCM (3×50 mL)
  5. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customthe crude product was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-9053bb02e3d541b88a3c1680b4b36fc4
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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