Ammonium fluoride → 5-Amino-3-[(2R,3R,5S)-3-(1-fluoro-1-methyl-ethyl)-5-(hydroxymethyl)tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione

HRID 60769

Reaction equation

HRID 60769 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=[O:40])[C:5]2[S:10][C:9](=[O:11])[N:8]([C@H:12]3[C@H:16]([C:17]([F:20])([CH3:19])[CH3:18])[CH2:15][C@@H:14]([CH2:21][O:22][Si](C(C)(C)C)(C4C=CC=CC=4)C4C=CC=CC=4)[O:13]3)[C:6]=2[N:7]=1.[NH4+].[F-]>CO>[NH2:1][C:2]1[NH:3][C:4](=[O:40])[C:5]2[S:10][C:9](=[O:11])[N:8]([C@H:12]3[C@H:16]([C:17]([F:20])([CH3:19])[CH3:18])[CH2:15][C@@H:14]([CH2:21][OH:22])[O:13]3)[C:6]=2[N:7]=1

Participants

4

Reactant 2

HCID 25516Ammonium fluorideHCID 1371902235-amino-3-[(2R,3R,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-3-(1-fluoro-1-methyl-ethyl)tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione2×

Product 1

HCID 1371086975-Amino-3-[(2R,3R,5S)-3-(1-fluoro-1-methyl-ethyl)-5-(hydroxymethyl)tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dioneYield 24.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 5-amino-3-[(2R,3R,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-3-(1-fluoro-1-methyl-ethyl)tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione (compound 40h, 66 mg, 0.12 mmol) and NH4F (133 mg, 3.6 mmol) in methanol was heated under reflux for 1.5 hrs. The resulting mixture was concentrated in vacuo and the residue was purified by preparative HPLC to afford 10 mg of 5-amino-3-[(2R,3R,5S)-3-(1-fluoro-1-methyl-ethyl)-5-(hydroxymethyl)tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione (Example 40) as a white solid.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 1.5 hrs
  3. concentrationThe resulting mixture was concentrated in vacuo
  4. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-a4d00bd2e89e427383ca0c2294c38e0b
Source dataset
uspto-grants-2016_09
Patent number
US09441008B2

Linked notes

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