Sodium Nitrite → HCID 178431867, compound

HRID 58304Notes

Reaction equation

N[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([NH:11][C@H:12]([C:14]2[N:15]=[C:16]3[S:30][CH:29]=[C:28]([CH3:31])[N:17]3[C:18](=[O:27])[C:19]=2[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[CH3:13])[N:3]=1.N([O-])=[O:33].[Na+]>C(O)(=O)C.O>[F:26][C:22]1[CH:21]=[C:20]([C:19]2[C:18](=[O:27])[N:17]3[C:28]([CH3:31])=[CH:29][S:30][C:16]3=[N:15][C:14]=2[C@@H:12]([NH:11][C:4]2[N:3]=[C:2]([OH:33])[N:10]=[C:9]3[C:5]=2[N:6]=[CH:7][NH:8]3)[CH3:13])[CH:25]=[CH:24][CH:23]=1

Participants

Conditions

Temperature: 20 °C

Procedure

A solution of 7-{(1S)-1-[(2-amino-9H-purin-6-yl)amino]ethyl}-6-(3-fluorophenyl)-3-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (27 mg, 62 μmol) in acetic acid (0.41 mL) and water (84 μL) at 0° C. was treated with a solution of sodium nitrite (13 mg, 0.19 mmol) in water (0.15 mL) dropwise and stirred at 0° C. for 30 minutes and at 20° C. for 16 hours. The reaction mixture was concentrated and purified by RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (7 mg, 20%) as a white solid. LCMS for C20H17FN7O2S (M+H)+: m/z=437.8. 1H NMR (300 MHz, DMSO-d6): δ 7.79 (br s, 1H), 7.68-7.61 (m, 1H), 7.50-7.38 (m, 3H), 7.23-7.14 (m, 2H), 7.06 (br s, 1H), 5.02-4.92 (m, 1H), 2.64 (s, 3H), 1.26 (d, J=6.7 Hz, 3H).

Workup

concentrationThe reaction mixture was concentrated
custompurified by RP-HPLC (XBridge C18 column
washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record: ord-64bf6080ac814c21801cc5743f4d8362
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434746B2

Reaction notes

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