1H-1,2,4-Triazole → 7-Cyclobutyl-5-iodo-imidazo[5,1-f][1,2,4]triazin-4-ylamine
Reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.P(Cl)(Cl)(Cl)=O.[CH:11]1([C:15]2[N:23]3[C:18](C(=O)NC=N3)=[C:17]([I:25])[N:16]=2)[CH2:14][CH2:13][CH2:12]1>N1C=CC=CC=1>[CH:11]1([C:15]2[N:23]3[C:18]([C:5]([NH2:1])=[N:4][CH:3]=[N:2]3)=[C:17]([I:25])[N:16]=2)[CH2:14][CH2:13][CH2:12]1Participants
Procedure
To a solution of 1,2,4-triazole (1.28 g, 18.59 mmol) in anhydrous pyridine (10 mL) was added phosphorus oxychloride (POCl3) (0.578 mL, 6.20 mmol) and stirred at rt for 15 min. This mixture was dropwise charged (3.5 min) with a solution of 7-cyclobutyl-5-iodo-3H imidazo[5,1-f][1,2,4]triazin-4-one (0.653 mg 2.07 mmol) in anhydrous pyridine (14 ml) and stirred for 1.5 h. The reaction mixture was cooled to 0° C. quenched with 2M NH3 in isopropanol (IPA) until basic then allowed to reach rt and stirred for an additional 2 h. The reaction mixture was filtered through a fritted Buchner funnel and washed with DCM. The filtrate was concentrated in vacuo and purified by chromatography on silica gel [eluting with 30% EtOAc in DCM] resulting in the title compound as an off-white solid; 1H NMR (CDCl3, 400 MHz) δ 1.93-2.04 (m, 1H), 2.05-2.18 (m, 1H), 2.35-2.45 (m, 2H), 2.49-2.62 (m, 2H), 4.00-4.12 (m, 1H), 7.82 (s, 1H); MS (ES+): m/z 316.08 (100) [MH+], HPLC: tR=2.59 min (MicromassZQ, polar—5 min).
Workup
- stirringstirred for 1.5 h
- temperatureThe reaction mixture was cooled to 0° C.
- customquenched with 2M NH3 in isopropanol (IPA) until basic
- customto reach rt
- stirringstirred for an additional 2 h
- filtrationThe reaction mixture was filtered through a fritted Buchner funnel
- washwashed with DCM
- concentrationThe filtrate was concentrated in vacuo
- custompurified by chromatography on silica gel [eluting with 30% EtOAc in DCM]
Sources & evidence
- ORD record
- ord-7ca4ea43cacb488d97c0b9052d358799
- Source dataset
- uspto-grants-2012_11
- Patent number
- US08314111B2
Reaction notes
Loading…