Trimethylsilyl triflate → (2R,3R,4R,5R)-4-(Acetyloxy)-2-[6-[(2,2-diphenylethyl)amino]-2-({[2-(1-piperidinyl)ethyl]amino}carbonyl)-9H-purin-9-yl]-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydro-3-furanyl acetate

HRID 1168298Notes

Reaction equation

HRID 1168298 reaction equation
[C:1]1([CH:7]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:8][NH:9][C:10]2[N:18]=[C:17]([C:19]([NH:21][CH2:22][CH2:23][N:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)=[O:20])[N:16]=[C:15]3[C:11]=2[N:12]=[CH:13][NH:14]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:36]([O:39][C@H:40]1[C@@H:44]([O:45][C:46](=[O:48])[CH3:47])[CH:43](OC(=O)C)[O:42][C@@H:41]1[C:53]1[N:54]=[N:55][N:56]([CH2:58][CH3:59])[N:57]=1)(=[O:38])[CH3:37].C[Si](OS(C(F)(F)F)(=O)=O)(C)C>ClC(Cl)(Cl)C.C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:46]([O:45][C@@H:44]1[C@H:40]([O:39][C:36](=[O:38])[CH3:37])[C@@H:41]([C:53]2[N:54]=[N:55][N:56]([CH2:58][CH3:59])[N:57]=2)[O:42][C@H:43]1[N:14]1[CH:13]=[N:12][C:11]2[C:15]1=[N:16][C:17]([C:19]([NH:21][CH2:22][CH2:23][N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)=[O:20])=[N:18][C:10]=2[NH:9][CH2:8][CH:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)(=[O:48])[CH3:47]

Participants

7

Reactant 3

HCID 65367Trimethylsilyl triflateHCID 11302289(2R,3R,4R)-4,5-bis(acetoxy)-2-(2-ethyl-2H-tetrazol-5-yl)tetrahydro-3-furanyl acetateHCID 1785234056-[(2,2-Diphenylethyl)amino]-N-[2-(1-piperidinyl)ethyl]-9H-purine-2-carboxamide

Product 1

HCID 70023610(2R,3R,4R,5R)-4-(Acetyloxy)-2-[6-[(2,2-diphenylethyl)amino]-2-({[2-(1-piperidinyl)ethyl]amino}carbonyl)-9H-purin-9-yl]-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydro-3-furanyl acetateYield 74.4%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 62781,1,1-TrichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 6-[(2,2-diphenylethyl)amino]-N-[2-(1-piperidinyl)ethyl]-9H-purine-2-carboxamide (Preparation 11) (0.2 g, 0.42 mmol) in 1,1,1-trichloroethane (10 ml) was treated with N,O-bis(trimethylsilylacetamide) (0.65 ml, 2.65 mmol) and the mixture was heated under reflux for 2 hours. The solvent was removed under reduced pressure and the residue was twice azeotroped with toluene. The residue was dissolved in toluene (5 ml) and treated sequentially with a solution of (2R,3R,4R)-4,5-bis(acetyloxy)-2-(2-ethyl-2H-tetrazol-5-yl)tetrahydro-3-furanyl acetate (WO-A-9967265) (0.175 g, 0.51 mmol) in toluene (5 ml) and then trimethylsilyltriflate (0.1 ml, 0.55 mmol). The mixture was heated under reflux for 3 hours and then allowed to stand at room temperature overnight. The solution was diluted with ethyl acetate (40 ml), washed sequentially with saturated aqueous sodium hydrogen carbonate solution (20 ml) and brine (20 ml) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (93:7 by volume) gradually changing to dichloromethane:methanol (90:10 by volume) to afford the title compound (0.235 g).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 hours
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was twice azeotroped with toluene
  5. dissolutionThe residue was dissolved in toluene (5 ml)
  6. temperatureThe mixture was heated
  7. temperatureunder reflux for 3 hours
  8. washwashed sequentially with saturated aqueous sodium hydrogen carbonate solution (20 ml) and brine (20 ml)
  9. customevaporated under reduced pressure
  10. customThe residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (93:7 by volume)

Sources & evidence

ORD record
ord-e703f46d7d814bcfa2bf1f00241bfc02
Source dataset
uspto-grants-2003_09
Patent number
US06624158B2

Reaction notes

Loading…