Sodium Nitrite → (1S,2S,3R,5S)-3-(7-Chloro-5-(Propylthio)-3H-[1,2,3]Triazolo[4,5-d]Pyrimidin-3-Yl)-5-(2-Hydroxyethoxy)Cyclopentane-1,2-Diol

HRID 923298Notes

Reaction equation

[NH2:1][C:2]1[C:3]([NH:13][C@@H:14]2[CH2:18][C@H:17]([O:19][CH2:20][CH2:21][OH:22])[C@@H:16]([OH:23])[C@H:15]2[OH:24])=[N:4][C:5]([S:9][CH2:10][CH2:11][CH3:12])=[N:6][C:7]=1[Cl:8].[N:25]([O-])=O.[Na+]>C(O)(=O)C.C(OCC)(=O)C>[Cl:8][C:7]1[C:2]2[N:1]=[N:25][N:13]([C@@H:14]3[CH2:18][C@H:17]([O:19][CH2:20][CH2:21][OH:22])[C@@H:16]([OH:23])[C@H:15]3[OH:24])[C:3]=2[N:4]=[C:5]([S:9][CH2:10][CH2:11][CH3:12])[N:6]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To a stirring solution of (1S,2S,3R,5S)-3-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol (OLACINA; 1.14 g, 3 mmol) in acetic acid (5 mL) was added sodium nitrite (0.23 g, 3.3 mmol) while maintaining the reaction temperature at 20-30° C. The reaction mixture was stirred for 30 minutes. It was then diluted with ethyl acetate (50 mL), washed with water (2×35 mL) and evaporated under reduced pressure. The crude product was triturated in hexane (20 mL) and filtered to give CLTOL as an off-white powder (1.00 g, 86% yield): 98 area % by HPLC; mp 98-107° C.; 13C NMR (CDCl3, 125 MHz) δ13.4, 22.0, 33.5, 33.7, 61.75, 61.77, 71.1, 74.9, 75.4, 82.0, 131.8, 150.7, 152.9, 171.8.

Workup

washwashed with water (2×35 mL)
customevaporated under reduced pressure
customThe crude product was triturated in hexane (20 mL)
filtrationfiltered

Sources & evidence

ORD record: ord-4c2ee70b4f114bef9c74f4d653d44340
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278972B2

Reaction notes

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