N-Iodosuccinimide → Benzyl 4-(8-chloro-1-iodoimidazo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate

HRID 449004Notes

Reaction equation

[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[O:18])[CH2:13][CH2:12]3)=[N:9][CH:10]=2)[CH:5]=[CH:6][N:7]=1.C1C(=O)N([I:34])C(=O)C1>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[C:3]2[N:4]([C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)=[O:18])[CH2:13][CH2:12]3)=[N:9][C:10]=2[I:34])[CH:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of benzyl 4-(8-chloroimidazo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate (1.31 g, 0.00354 mol) in DMF (0.6 mL) was added NIS (1.6 g, 0.0071 mol). The reaction mixture was left to stir at 55° C. for 20 h. then the mixture was diluted with EtOAc (20 mL), washed with water (2×40 mL) and brine, then dried over Na2SO4 and concentrated in vacuo. The crude reaction mixture was chromatographed over silica gel eluting with hexane hexane:EtOAc 1:1 yielding 1.63 g of desired product. 1H NMR (400 MHz, CDCl3): δ 1.95-2.04 (m, 4H), 3.02-3.15 (m, 3H), 4.29-4.32 (m, 2H), 5.15 (s, 2H), 7.32 (d, J=5.2 Hz, 1H), 7.34-7.37 (m, 5H), 7.66 (d, J=5.2 Hz, 1H). MS (ES+): m/z 497.03 [MH+].

Workup

waitThe reaction mixture was left
washwashed with water (2×40 mL) and brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe crude reaction mixture
customwas chromatographed over silica gel eluting with hexane hexane:EtOAc 1:1 yielding 1.63 g of desired product

Sources & evidence

ORD record: ord-c4a156eba95145f7bce0b89c61151dd0
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481733B2

Reaction notes

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