Pyridine → Carbonic acid (1S,4R)-4-[2-chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-cyclopent-2-enyl ester ethyl ester

HRID 1697002Notes

Reaction equation

HRID 1697002 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[CH2:15][C@H:14]([OH:16])[CH:13]=[CH:12]2)=[C:4]([NH:17][CH2:18][CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:3]=1.N1C=CC=CC=1.Cl[C:39]([O:41][CH2:42][CH3:43])=[O:40]>C1COCC1>[CH2:42]([O:41][C:39](=[O:40])[O:16][C@H:14]1[CH2:15][C@@H:11]([N:8]2[CH:7]=[N:6][C:5]3[C:9]2=[N:10][C:2]([Cl:1])=[N:3][C:4]=3[NH:17][CH2:18][CH:19]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:12]=[CH:13]1)[CH3:43]

Participants

5

Reactant 3

HCID 1049PyridineHCID 10928Ethyl chloroformateHCID 86622638(1S,4R)-4-[2-Chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-cyclopent-2-enol

Product 1

HCID 86622637Carbonic acid (1S,4R)-4-[2-chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-cyclopent-2-enyl ester ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(1S,4R)-4-[2-Chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-cyclopent-2-enol (3.00 g, 6.95 mmol) is placed in an oven-dried flask under an atmosphere of argon. Dry THF (100 ml) is added followed by dry pyridine (1.10 g, 13.90 mmol). Ethyl chloroformate (3.02 g, 27.80 mmol) is added slowly and the reaction mixture is stirred at room temperature. The reaction is shown to be complete by TLC after 4 hours. The solvent is removed in vacuo and the residue is partitioned between dichloromethane (200 ml) and 10% citric acid (200 ml). The organic layer is washed with water (150 ml) and brine (150 ml), dried over MgSO4, filtered and the solvent is removed in vacuo. The title compound is obtained after purification by flash column chromatography (silica, iso-hexane/ethyl acetate 2:1). 1H nmr (CDCl3, 400 MHz); 7.70(br s, 1H), 7.35-7.15(m, 10H), 6.35(m, 1H), 6.15(m, 1H), 5.80(m, 1H), 5.65(m, 2H), 4.35(t, 1H), 4.25(m, 2H), 4.20(q, 2H), 3.10(m, 1H), 1.95(d, 1H), 1.30(t, 3H), MS (ES+) m/e 504 (MH+).

Workup

  1. customThe solvent is removed in vacuo
  2. customthe residue is partitioned between dichloromethane (200 ml) and 10% citric acid (200 ml)
  3. washThe organic layer is washed with water (150 ml) and brine (150 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvent is removed in vacuo

Sources & evidence

ORD record
ord-e7860ce939194ad18944fab5cf0b65c6
Source dataset
uspto-grants-2012_04
Patent number
US08163754B2

Reaction notes

Loading…