Dimethylformamide → 3-(8-Chloro-1-iodoimidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol
Reaction equation
[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:11]3[CH2:14][C:13]([CH3:16])([OH:15])[CH2:12]3)=[N:9][CH:10]=2)[CH:5]=[CH:6][N:7]=1.C1C(=O)N([I:24])C(=O)C1.CN(C=O)C>>[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:11]3[CH2:12][C:13]([CH3:16])([OH:15])[CH2:14]3)=[N:9][C:10]=2[I:24])[CH:5]=[CH:6][N:7]=1Participants
Conditions
- Temperature
- 60 °C
Procedure
3-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol (2.20 g, 9.26 mmol) and NIS (2.71 g, 12.0 mmol) were dissolved in DMF (36.6 mL, 0.472 mol) and stirred at 60° C. for 4 h. The mixture was then concentrated in vacuo and the residue reconstituted in EtOAc (100 mL). This solution was washed with sodium bicarbonate (2×20 mL) and these washes back-extracted with EtOAc (2×20 mL). The organic layers were combined, dried with sodium sulfate, filtered and concentrated in vacuo. The crude solid was purified by chromatography over silica gel eluting with 1:1 EtOAc:hexanes to afford desired product. 1H-NMR (400 MHz, CDCl3) δ ppm 1.53 (s, 3 H), 2.72-2.59 (m, 4 H), 3.37-3.29 (m, 1 H), 7.32 (d, J=4.91 Hz, 1 H) and 7.60 (d, J=4.96 Hz, 1 H). MS (ES+): m/z 363.95 and 365.91 [MH+].
Workup
- concentrationThe mixture was then concentrated in vacuo
- washThis solution was washed with sodium bicarbonate (2×20 mL)
- extractionthese washes back-extracted with EtOAc (2×20 mL)
- dry with materialdried with sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude solid was purified by chromatography over silica gel eluting with 1:1 EtOAc
Sources & evidence
- ORD record
- ord-82429a4566ff4e7e85a2a861f4a6c4e6
- Source dataset
- uspto-grants-2010_01
- Patent number
- US07651687B2
Reaction notes
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