Dimethylbarbituric acid → HCID 68283497, compound

HRID 2408697Notes

Reaction equation

HRID 2408697 reaction equation
C([O:4][C:5]1[CH:6]=[C:7]([CH:15]([OH:32])[CH2:16][N:17]2[C:25]3[CH:24]=[CH:23][C:22]([CH3:26])=[CH:21][C:20]=3[C:19]3[CH2:27][N:28]([CH3:31])[CH2:29][CH2:30][C:18]2=3)[CH:8]=[CH:9][C:10]=1[O:11]CC=C)C=C.CN1C(=O)CC(=O)N(C)C1=O>CO.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>[CH3:31][N:28]1[CH2:29][CH2:30][C:18]2[N:17]([CH2:16][CH:15]([C:7]3[CH:6]=[C:5]([OH:4])[C:10]([OH:11])=[CH:9][CH:8]=3)[OH:32])[C:25]3[CH:24]=[CH:23][C:22]([CH3:26])=[CH:21][C:20]=3[C:19]=2[CH2:27]1

Participants

5

Reactant 2

HCID 69860Dimethylbarbituric acidHCID 68283830HCID 68283830, compound

Product 1

HCID 68283497HCID 68283497, compoundYield 39.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Procedure

To a solution of 1-(3,4-Bis-allyloxy-phenyl)-2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-ethanol (500 mg, 1.15 mmol) in 10 mL MeOH was purged with nitrogen for 10 min. 1,3-Dimethylbarbituric acid (903 mg, 5.79 mmol) and Pd(PPh3)4 (80 mg, 0.069 mmol) were added under nitrogen and the mixture stirred for 30 min at RT. After the complete conversion of starting material (TLC and LCMS), the MeOH was removed under reduced pressure. 100 mL of saturated sodium bicarbonate was added and the mixture was extracted with EtOAc (3×100 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated. The resultant crude product was purified by HPLC to obtain 160 mg of 4-[2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-hydroxy-ethyl]-benzene-1,2-diol. 1H NMR (CD3OD, Free base) δ (ppm): 7.3 (d, 1H), 7.2 (s, 1H), 7.05 (dd, 1H), 6.7 (d, 1H), 6.6 (s, 1H), 6.53 (d, 1H), 4.8 (t, 1H), 4.21 (m, 3H), 4.05 (dd, 1H), 3.34 (m, 1H), 3.3 (m, 1H), 2.88 (dt, 1H), 2.81 (s, 3H), 2.5 (dt, 1H), 2.4 (s, 3H). Separation by chiral HPLC provides enantiomers II-88a-b.

Workup

  1. customAfter the complete conversion of starting material (TLC and LCMS), the MeOH was removed under reduced pressure
  2. addition100 mL of saturated sodium bicarbonate was added
  3. extractionthe mixture was extracted with EtOAc (3×100 mL)
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe resultant crude product was purified by HPLC

Sources & evidence

ORD record
ord-a9448d272c954513909f85c73c48d8fe
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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