Sodium Iodide → 2-(4-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)piperidin-1-yl)acetamide

HRID 1946112Notes

Reaction equation

Cl.[CH2:2]([C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[N:15]3[CH3:18])=[C:11]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[N:10]=2)[C:7]2[CH:31]=[CH:32][CH:33]=[CH:34][C:6]=2[N:5]=1)[CH3:3].Br[CH2:36][C:37]([NH2:39])=[O:38].[I-].[Na+].C([O-])([O-])=O.[K+].[K+]>CC#N.CCOC(C)=O>[CH2:2]([C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH:19]4[CH2:20][CH2:21][N:22]([CH2:36][C:37]([NH2:39])=[O:38])[CH2:23][CH2:24]4)[N:15]3[CH3:18])=[C:11]([N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[N:10]=2)[C:7]2[CH:31]=[CH:32][CH:33]=[CH:34][C:6]=2[N:5]=1)[CH3:3]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-8-piperidin-4-yl-9H-purine hydrochloride (150 mg, 0.31 mmol), 2-bromoacetamide (45 mg, 0.33 mmol), sodium iodide (5 mg, 0.03 mmol) and K2CO3 (90 mg, 0.65 mmol) in MeCN (3 mL) was heated to 50° C. for 2 h in a sealed tube. The reaction mixture was diluted with EtOAc, filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-30%) affording 677 (119 mg, 76%). LCMS (method I): RT 2.40 min, [M+H]+ 504.2. 1H NMR (DMSO, 400 MHz): δ 8.02-7.98 (1 H, m), 7.64-7.63 (1 H, m), 7.25-7.24 (4 H, m), 4.27 (4 H, brd s), 3.82-3.72 (7 H, m), 3.35-3.30 (2 H, m), 3.26 (2 H, q, J=7.45 Hz), 3.11-2.90 (4 H, m), 2.38-2.31 (1 H, m), 1.97 (4 H, s), 1.33 (3 H, t, J=7.44 Hz)

Workup

filtrationfiltered
concentrationconcentrated in vacuo
customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-30%)

Sources & evidence

ORD record: ord-cd580736239341ac8cd784f41df36ed7
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08394796B2

Reaction notes

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