Water → HCID 67079134, compound

HRID 480156Notes

Reaction equation

HRID 480156 reaction equation
[O:1]=[C:2]1[N:10]([CH2:11][CH2:12][CH3:13])[C:9]2[N:8]=[C:7]([C:14]34[CH2:21][CH2:20][C:17]([C:22](=[S:24])[NH2:23])([CH2:18][CH2:19]3)[CH2:16][CH2:15]4)[NH:6][C:5]=2[C:4](=[O:25])[N:3]1[CH2:26][CH2:27][CH3:28].Br[CH2:30][C:31](=O)[C:32]([O:34][CH2:35][CH3:36])=[O:33].N1C=CC=CC=1.O>C1COCC1>[CH2:35]([O:34][C:32]([C:31]1[N:23]=[C:22]([C:17]23[CH2:20][CH2:21][C:14]([C:7]4[NH:6][C:5]5[C:4](=[O:25])[N:3]([CH2:26][CH2:27][CH3:28])[C:2](=[O:1])[N:10]([CH2:11][CH2:12][CH3:13])[C:9]=5[N:8]=4)([CH2:19][CH2:18]2)[CH2:15][CH2:16]3)[S:24][CH:30]=1)=[O:33])[CH3:36]

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 66144Ethyl bromopyruvateHCID 86591745HCID 86591745, compound

Product 1

HCID 67079134HCID 67079134, compoundYield 88.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carbothioic acid amide (20 mg, 50 μmol) and KLCO3 (8.0 eq, 400 μmol) in THF (5 ml) was stirred vigorously for 5 min and ethyl bromopyruvate (29 mg, 150 μmol) was added neat via syringe. The resulting, pale yellow solution was stirred at rt for 1 h, cooled to 0° C. with the aid of an ice bath and treated sequentially with pyridine (8.0 eq, 400 μmol) and (F3CCO)2O (4.0 eq, 42 mg, 200 μmol). The resulting deep red solution was allowed to reach ambient temperature overnight. Following the addition of water (4 ml), the mixture was concentrated in vacuo and extracted with CH2Cl2 (2×10 ml). The combined organic phases were washed with 2 N HCl, dried (Na2SO4), filtered and concentrated in vacuo. The solution was purified by radial chromatography (1 mm plate) using 2-5% MeOH in CH2Cl2 as eluent to afford a white solid (22 mg, 88%). MS: 500 (MH+).

Workup

  1. stirringThe resulting, pale yellow solution was stirred at rt for 1 h
  2. waitto reach ambient temperature overnight
  3. concentrationthe mixture was concentrated in vacuo
  4. extractionextracted with CH2Cl2 (2×10 ml)
  5. washThe combined organic phases were washed with 2 N HCl
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe solution was purified by radial chromatography (1 mm plate)

Sources & evidence

ORD record
ord-15407ffc33ff408c828eb97b1f809ab5
Source dataset
uspto-grants-2003_11
Patent number
US06649600B1

Reaction notes

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