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

HRID 40670

반응식

HRID 40670 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 21735183Dimethylformamide toluene용매

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온도
150 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-68a88dca70fb4c9daa1ea5cb4026c9b2
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530468B2

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