Triphenylphosphine → 6-(2,2-Diphenyl-ethylamino)-9-((1R,4S)-4-hydroxy-cyclopent-2-enyl)-9H-purine-2-carboxylic acid methyl ester

HRID 1641896Notes

Reaction equation

HRID 1641896 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:13]=[C:12]2[C:8]([N:9]=[CH:10][NH:11]2)=[C:7]([NH:14][CH2:15][CH:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:6]=1)=[O:4].[H-].[Na+].CC([O:34][C@H:35]1[CH:39]=[CH:38][C@@H:37](O)[CH2:36]1)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>>[CH3:1][O:2][C:3]([C:5]1[N:13]=[C:12]2[C:8]([N:9]=[CH:10][N:11]2[C@@H:38]2[CH2:39][C@H:35]([OH:34])[CH:36]=[CH:37]2)=[C:7]([NH:14][CH2:15][CH:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:6]=1)=[O:4]

Participants

5

Reactant 4

HCID 11776TriphenylphosphineHCID 24758Sodium hydrideHCID 10154103rac-(1R,4S)-4-hydroxycyclopent-2-en-1-yl acetateHCID 178418823HCID 178418823, compound

Product 1

HCID 666305706-(2,2-Diphenyl-ethylamino)-9-((1R,4S)-4-hydroxy-cyclopent-2-enyl)-9H-purine-2-carboxylic acid methyl ester

Procedure

6-(2,2-Diphenyl-ethylamino)-9H-purine-2-carboxylic acid methyl ester (Intermediate DA) (10.8 g 28.9 mmol) is placed in an oven-dried flask under an atmosphere of argon. Dry deoxygenated tetrahydrofuran (200 mL) and dry dimethyl sulfoxide (5 mL) are added and the suspension is cooled on an ice-bath. Sodium hydride 95% (0.69 g, 28.9 mmol) is then slowly added and the solution is stirred at room temperature for 30 minutes. (1S,4R)-cis 4-Acetoxy-2-cyclopenten-1-ol (3.9 g, 27.5 mmol), triphenylphosphine (1.08 g, 4.13 mmol) and tetrakis(triphenyl-phosphine)palladium(0) (1.27 g, 1.38 mmol) are placed in an oven-dried flask under an atmosphere of argon. Dry deoxygenated tetrahydrofuran (20 mL) is added and stirred at room temperature for 30 minutes. This solution is added to the anion solution via syringe and is then stirred at 50° C. for 6 hours. The reaction mixture is allowed to cool and the solvent is removed in vacuo. The title compound is obtained after purification by flash column chromatography (silica, 0% to 10% MeOH in DCM). 1H NMR (MeOD, 400 MHz); 8.15 (s, 1H), 7.40-7.15 (m, 10H), 6.30 (m, 1H), 5.95 (m, 1H), 5.60 (m, 1H), 5.50 (m, 1H), 4.85 (m, 1H), 4.55 (m, 1H), 4.30 (m 2H), 4.00 (s, 2H), 2.65 (s, 3H).

Workup

  1. customDry
  2. customdeoxygenated tetrahydrofuran (200 mL) and dry dimethyl sulfoxide (5 mL)
  3. additionare added
  4. temperaturethe suspension is cooled on an ice-bath
  5. customDry
  6. customdeoxygenated tetrahydrofuran (20 mL)
  7. additionis added
  8. stirringstirred at room temperature for 30 minutes
  9. additionThis solution is added to the anion solution via syringe
  10. stirringis then stirred at 50° C. for 6 hours
  11. temperatureto cool
  12. customthe solvent is removed in vacuo

Sources & evidence

ORD record
ord-3ae4b1c448224d888b955098da1b45a0
Source dataset
uspto-grants-2012_02
Patent number
US08114877B2

Reaction notes

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