Carbon Dioxide → HCID 69662067, compound

HRID 892109Notes

Reaction equation

HRID 892109 reaction equation
[CH2:1]([N:8]1[C:16]2[C:15]3=[N:17][C@H:18]([CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:19][N:14]3[C:13](=[O:27])[N:12]([CH2:28][CH2:29][CH3:30])[C:11]=2[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[C:39](=[O:41])=[O:40].Cl>O1CCCC1.C1CCCCC1>[CH2:1]([N:8]1[C:16]2[C:15]3=[N:17][C@H:18]([CH2:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:19][N:14]3[C:13](=[O:27])[N:12]([CH2:28][CH2:29][CH3:30])[C:11]=2[N:10]=[C:9]1[C:39]([OH:41])=[O:40])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 280Carbon Dioxide2×HCID 313Hydrochloric AcidHCID 2724682Lithium diisopropylamideHCID 23600250HCID 23600250, compound

Product 1

HCID 69662067HCID 69662067, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8078CyclohexaneSolvent

Procedure

Compound 35a (3.95 g, 9.90 mmol) obtained in Example 35 was dissolved in tetrahydrofuran (100 mL), to the solution was added a 1.50 mol/L solution (9.9 mL) of lithium diisopropylamide (14.9 mmol, 1.5 equivalents) in cyclohexane at −78° C., and then the mixture was stirred for 1 hour. Into the reaction solution was poured carbon dioxide generated from dry ice and the mixture was stirred at room temperature for 1 hour. To the reaction solution was added 1 mol/L aqueous hydrochloric acid and the mixture was extracted with chloroform. The organic layer was washed with saturated aqueous sodium chloride and dried. The solvent was evaporated, and the residue was purified by silica gel column chromatography (chloroform:methanol=95:5 to 10:1). To the residue were added acetone and diethyl ether, and the deposited crystals were collected by filtration to obtain (R)-1,8-dibenzyl-2-carboxy-7,8-dihydro-4-(n-propyl)-1H-imidazo[2,1-i]purin-5(4H)-one (Compound 47a, 1.13 g, 26%). To Compound 47a (740 mg, 1.67 mmol) was added thionyl chloride (10.0 mL, 137 mmol, 82 equivalents) and the mixture was stirred at 60° C. for 2 hours. The reaction solution was concentrated under reduced pressure, and then to the reaction residue was added methanol (3 mL). The mixture was concentrated and the residue was directly purified by silica gel column chromatography (chloroform:methanol=95:5) to obtain the title compound (211 mg, 28%).

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hour
  2. extractionthe mixture was extracted with chloroform
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. customdried
  5. customThe solvent was evaporated
  6. customthe residue was purified by silica gel column chromatography (chloroform:methanol=95:5 to 10:1)
  7. additionTo the residue were added acetone and diethyl ether
  8. filtrationthe deposited crystals were collected by filtration

Sources & evidence

ORD record
ord-92db19e0f6f147c58a5d219e36902709
Source dataset
uspto-grants-2006_02
Patent number
US07005430B2

Reaction notes

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