Acetic Acid → 2-(((3aR,4S,6R,6aS)-6-(7-Chloro-5-(propylthio)-3H-1,2,3-triazolo(4,5-d)pyrimidin-3-yl)tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl)oxy)ethanol

HRID 2404973Notes

Reaction equation

HRID 2404973 reaction equation
[N:1]([O-])=O.[Na+].[NH2:5][C:6]1[C:7]([NH:17][C@H:18]2[C@@H:22]3[O:23][C:24]([CH3:27])([CH3:26])[O:25][C@@H:21]3[C@@H:20]([O:28][CH2:29][CH2:30][OH:31])[CH2:19]2)=[N:8][C:9]([S:13][CH2:14][CH2:15][CH3:16])=[N:10][C:11]=1[Cl:12].C(O)(=O)C.C(=O)([O-])[O-].[K+].[K+]>O.C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:12][C:11]1[C:6]2[N:5]=[N:1][N:17]([C@H:18]3[C@@H:22]4[O:23][C:24]([CH3:26])([CH3:27])[O:25][C@@H:21]4[C@@H:20]([O:28][CH2:29][CH2:30][OH:31])[CH2:19]3)[C:7]=2[N:8]=[C:9]([S:13][CH2:14][CH2:15][CH3:16])[N:10]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 102021862-(((3aR,4S,6R,6aS)-6-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanolHCID 23668193Sodium Nitrite

Product 1

HCID 210357742-(((3aR,4S,6R,6aS)-6-(7-Chloro-5-(propylthio)-3H-1,2,3-triazolo(4,5-d)pyrimidin-3-yl)tetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl)oxy)ethanolYield 45.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A solution of sodium nitrite (148 mg, 2.14 mmol, 1.12 equiv.) in water (1 mL) was added to a solution of 2-((3aR,4S,6R,6aS)-6-(5-amino-6-chloro-2-(propylthio)pyrimidin-4-ylamino)-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yloxy)ethanol (800 mg, 1.91 mmol, 1.00 equiv.) and acetic acid (680 mg, 11.33 mmol, 5.90 equiv.) in toluene (9 mL). The resulting solution was stirred at about 20° C. for about 30 minutes, and then the pH value of the solution was adjusted to 8-9 by adding potassium carbonate. Following standard extractive workup with ethyl acetate (3×10 mL), the resulting residue was purified by silica gel column (ethyl acetate/petroleum ether (1:10)) to give the title product as a yellow oil (370 mg; yield=45%). 1H NMR (300 MHz, CDCl3) δ: 5.54-5.56 (q, J1=2.4 Hz, J2=6.3 Hz, 1H), 5.21-5.25 (m, 1H), 4.90 (d, J=6.3 Hz, 1H), 4.05-4.09 (m, 1H), 3.50-3.66 (m, 4H), 3.23 (t, J=7.5 Hz, 2H), 2.68-2.72 (m, 1H), 2.58 (m, 1H), 1.81-1.89 (m, 2H), 1.57 (s, 3H), 1.39 (s, 3H), 1.12, (t, J=7.5 Hz, 3H).

Workup

  1. customthe resulting residue was purified by silica gel column (ethyl acetate/petroleum ether (1:10))

Sources & evidence

ORD record
ord-480138d7440840269e50514e552efab5
Source dataset
uspto-grants-2014_08
Patent number
US08802850B2

Reaction notes

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