5-Aminopyrazine-2-carbonitrile → 5-(1-(4-methoxybenzyl)-1H-imidazo[4,5-c]pyridin-6-ylamino)pyrazine-2-carbonitrile

HRID 40670

反応式

HRID 40670 の反応式
[NH2:1][C:2]1[CH:7]=[N:6][C:5]([C:8]#[N:9])=[CH:4][N:3]=1.CC(C)([O-])C.[Na+].[CH3:16][O:17][C:18]1[CH:34]=[CH:33][C:21]([CH2:22][N:23]2[C:31]3[CH:30]=[C:29](Br)[N:28]=[CH:27][C:26]=3[N:25]=[CH:24]2)=[CH:20][CH:19]=1>CN(C=O)C.C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:16][O:17][C:18]1[CH:19]=[CH:20][C:21]([CH2:22][N:23]2[C:31]3[CH:30]=[C:29]([NH:1][C:2]4[N:3]=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=4)[N:28]=[CH:27][C:26]=3[N:25]=[CH:24]2)=[CH:33][CH:34]=1

参加物

6

反応物 3

HCID 139252945-Aminopyrazine-2-carbonitrileHCID 23676156Sodium t-butoxideHCID 569264661-(4-methoxybenzyl)-6-bromo-1H-imidazo[4,5-c]pyridine

生成物 1

HCID 442043575-(1-(4-methoxybenzyl)-1H-imidazo[4,5-c]pyridin-6-ylamino)pyrazine-2-carbonitrile収率 40%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 21735183Dimethylformamide toluene溶媒

反応条件

温度
150 °C

実験手順

Palladium (II) acetate (3.5 mg, 16 μmol) was added to (±)-2,2″-bis(diphenylphosphino)-1,1″-binaphthalene (59 mg, 94 μmol) in DMF/toluene (1:2) and the resulting mixture was degassed under a stream of nitrogen gas for 10 minutes. 2-Amino-5-cyanopyrazine (19 mg, 0.16 mmol), sodium tert-butoxide (45 mg, 0.47 mmol) and 1-(4-methoxybenzyl)-6-bromo-1H-imidazo[4,5-c]pyridine (50 mg, 0.16 mmol) were added and the mixture was degassed for a further 5 minutes before heating at 150° C. for 30 minutes using microwave irradiation. The reaction mixture was partitioned between water and dichloromethane. The aqueous phase extracted with dichloromethane. The combined organic layers were dried (Na2SO4) and concentrated. The residue was dissolved in methanol, passed through a PS-Thiol column and concentrated. The product was purified using preparative HPLC to give the title compound (22.4 mg, 40%). 1H NMR (d6-DMSO, 400 MHz) δ 10.84 (br s, 1H), 8.77 (d, 1H, J=1.3 Hz), 8.74 (m, 2H), 8.49 (s, 1H), 8.17 (s, 1H), 7.34 (m, 2H), 5.41 (s, 2H), 3.72 (s, 3H). LCMS (2) Rt=2.32 min; m/z (ESI+) 358 (MH+), (ESI−) 356 (M−H).

後処理

  1. customthe resulting mixture was degassed under a stream of nitrogen gas for 10 minutes
  2. customthe mixture was degassed for a further 5 minutes
  3. custommicrowave irradiation
  4. customThe reaction mixture was partitioned between water and dichloromethane
  5. extractionThe aqueous phase extracted with dichloromethane
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in methanol
  9. concentrationconcentrated
  10. customThe product was purified

出典と根拠

ORDレコード
ord-68a88dca70fb4c9daa1ea5cb4026c9b2
出典データセット
uspto-grants-2013_09
特許番号
US08530468B2

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