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 528035노트

반응식

HRID 528035 반응식
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

참가 물질

6

반응물 4

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 668020361-(1-(8-bromo-9-methyl-9H-purin-6-yl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one

생성물 1

HCID 569483291-{1-[8-(1H-imidazol-1-yl)-9-methyl-9H-purin-6-yl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one수율 48.1%

시약·촉매·용매 1

HCID 702Ethanol용매

반응 조건

온도
100 °C

실험 절차

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+).

후처리

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

출처 및 근거

ORD 기록
ord-728cbffa77ad425faeb7b469a6dca5e7
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346807B2

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