Imidazole → 1-{1-[8-(1H-imidazol-1-yl)-9-methyl-9H-purin-6-yl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one

HRID 528035Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

1-[1-(8-Bromo-9-methyl-9H-purin-6-yl)piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one (50 mg, 0.12 mmol) was dissolved in ethanol (1 mL). To this solution was added imidazole (24 mg, 0.35 mmol) and diisopropylethylamine (39 μL, 0.23 mmol). This mixture was irradiated in the microwave at 180° C. for 6 hours. The ethanol was removed in vacuo and replaced by DMA (1 mL). To this solution was added 1 equiv. of sodium hydride. After heating to 100° C. for 1 hour, the mixture was filtered and purified by prep HPLC to obtain 24 mg of the desired product. 1H NMR (400 MHz, DMSO-d6): δ 10.85 (s, 1H), 8.39-8.28 (m, 1H), 8.27-8.16 (m, 1H), 7.78 (m, 1H), 7.18 (m, 1H), 7.14 (m, 1H), 6.99-6.82 (m, 3H), 5.47 (s, 1H), 4.63-4.40 (m, 1H), 3.67 (s, 3H), 3.22 (m, 3H), 2.42-2.20 (m, 2H), 1.80 (m, 2H). EI (MS) for C21H21N9O, found 416 (MH+).

Workup

customThis mixture was irradiated in the microwave at 180° C. for 6 hours
customThe ethanol was removed in vacuo
filtrationthe mixture was filtered
custompurified by prep HPLC

Sources & evidence

ORD record: ord-728cbffa77ad425faeb7b469a6dca5e7
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346807B2

Reaction notes

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