Diisopropylamine → {2-Chloro-9-[(1R,4S)-4-(di-Boc-amino)-cyclopent-2-enyl]-9H-purin-6-yl}-(2,2-diphenyl-ethyl)amine

HRID 2382356Notes

Reaction equation

HRID 2382356 reaction equation
[C:1]([N:8]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:9]1[CH2:13][C@@H:12]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([Cl:24])=[N:18][C:19]=3Cl)[C@H:11](O)[C@@H:10]1O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(NC(C)C)(C)C.[C:41]1([CH:47]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH2:48][NH2:49])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C1COCC1>[Cl:24][C:17]1[N:16]=[C:15]2[C:20]([N:21]=[CH:22][N:14]2[C@@H:12]2[CH2:13][C@H:9]([N:8]([C:27]([O:29][C:30]([CH3:32])([CH3:33])[CH3:31])=[O:28])[C:1]([O:3][C:4]([CH3:5])([CH3:7])[CH3:6])=[O:2])[CH:10]=[CH:11]2)=[C:19]([NH:49][CH2:48][CH:47]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[N:18]=1

Participants

5

Reactant 3

HCID 7912DiisopropylamineHCID 775752,2-DiphenylethylamineHCID 57777515(1S,2R,3S,5R)-3-(di-tert-butoxycarbonylamino)-5-(2,6-dichloro-purin-9-yl)-cyclopentane-1,2-diol

Product 1

HCID 59418857{2-Chloro-9-[(1R,4S)-4-(di-Boc-amino)-cyclopent-2-enyl]-9H-purin-6-yl}-(2,2-diphenyl-ethyl)amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

(1S,2R,3S,5R)-3-(Di-Boc-amino)-5-(2,6-dichloro-purin-9-yl)-cyclopentane-1,2-diol (13.0 g, 27.66 mmol) is dissolved in THF (250 ml) under an atmosphere of argon. Diisopropylamine (4.28 g, 33.19 mmol) is added followed by 2,2-diphenylethylamine (6.0 g, 30.43 mmol) and the reaction mixture is stirred at 50° C. The reaction is shown to be complete by LCMS after 18 hours. The solvent is removed in vacuo and the reaction mixture is partitioned between dichloromethane (250 ml) and 0.1M HCl (250 ml). The organic layer is washed with water (200 ml) and brine (200 ml), dried over MgSO4, filtered and the solvent is removed in vacuo to give the title compound. 1H nmr (CDCl3, 400 MHz); 8.05 (s, 1H), 7.30-7.10 (m, 10H), 6.00 (m, 1H), 5.70 (m, 2H), 5.60 (m, 1H), 5.20 (m, 1H), 4.30 (m, 1H), 4.20 (m, 1H), 3.65 (m, 1H), 3.05 (m, 1H), 2.00 (m, 1H), 1.70 (m, 1H), 1.40 (s, 18H), MS (ES+) m/e 631 (MH+).

Workup

  1. customThe solvent is removed in vacuo
  2. customthe reaction mixture is partitioned between dichloromethane (250 ml) and 0.1M HCl (250 ml)
  3. washThe organic layer is washed with water (200 ml) and brine (200 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvent is removed in vacuo

Sources & evidence

ORD record
ord-3c13defab00642a491e5c664271dcc9c
Source dataset
uspto-grants-2012_09
Patent number
US08258141B2

Reaction notes

Loading…