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N-Acetylhomopiperazine → 1-(4-(5-amino-6-(6-methyl-1H-benzo[d]imidazol-2-yl)pyrazin-2-yl)-1,4-diazepan-1-yl)ethanone

HRID 1959336
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HRID 1959336 반응식
Br[C:2]1[N:3]=[C:4]([C:9]2[NH:13][C:12]3[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:11]=3[N:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.[N:19]1([C:26](=[O:28])[CH3:27])[CH2:25][CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>CN1C(=O)CCC1>[NH2:8][C:5]1[N:6]=[CH:7][C:2]([N:22]2[CH2:23][CH2:24][CH2:25][N:19]([C:26](=[O:28])[CH3:27])[CH2:20][CH2:21]2)=[N:3][C:4]=1[C:9]1[NH:13][C:12]2[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:11]=2[N:10]=1
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참가 물질

4

반응물 2

HCID 4186202N-AcetylhomopiperazineHCID 580842975-bromo-3-(6-methyl-1H-benzo[d]imidazol-2-yl)pyrazin-2-amine

생성물 1

HCID 461988041-(4-(5-amino-6-(6-methyl-1H-benzo[d]imidazol-2-yl)pyrazin-2-yl)-1,4-diazepan-1-yl)ethanone수율 56.3%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

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온도
190 °C

실험 절차

A mixture of 5-bromo-3-(6-methyl-1H-benzimidazol-2-yl)pyrazin-2-amine (100 mg, 0.3288 mmol) and 1-(1,4-diazepan-1-yl)ethanone (701 mg, 4.932 mmol) in NMP (200.0 μL) was heated at 190° C. in the microwave for 2 hours. The reaction mixture was partitioned between DCM and water and the organics separated and concentrated to dryness. The resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound (67.7 mg, 54% Yield). 1H NMR (400.0 MHz, DMSO) d 1.80-1.94 (2H, m), 1.78 (3H, s), 2.43-2.46 (3H, s), 3.40 (2H, m), 3.63-3.83 (5H, m), 3.92 (1H, m), 7.04-7.11 (3H, m), 7.38-7.59 (2H, m), 7.90 (1H, m), 12.37 (1H, m) ppm; MS (ES+) 366

후처리

  1. customThe reaction mixture was partitioned between DCM and water
  2. customthe organics separated
  3. concentrationconcentrated to dryness
  4. customThe resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]
  5. customThe fractions were collected
  6. customfreeze-dried

출처 및 근거

ORD 기록
ord-d205666ff04c459b9cff696ab5bba166
출처 데이터셋
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08410112B2

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