p-Toluenesulfonic acid → 4-(6-bromo-1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine

HRID 1398504노트

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HRID 1398504 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[NH:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=1.[CH:17](OC)(OC)OC.CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>C1COCC1.CO>[Br:8][C:5]1[CH:6]=[CH:7][C:2]2[N:1]=[CH:17][N:9]([C:10]3[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=3)[C:3]=2[CH:4]=1

참가 물질

7

반응물 4

HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformate2회HCID 516892Sodium BicarbonateHCID 681818104-N-(2-amino-5-bromophenyl)pyrimidine-2,4-diamine

생성물 1

HCID 681819584-(6-bromo-1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

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온도
70 °C

실험 절차

To a solution of 4-N-(2-amino-5-bromophenyl)pyrimidine-2,4-diamine (750 mg, 2.68 mmol) in mixture of methanol (7 mL) and THF (30 mL) was added trimethyl orthoformate (8.81 ml, 80.32 mmol) and TsOH (0.04 ml, 0.27 mmol). The reaction mixture was stirred at 70° C. for 1 h. Then another portion of trimethyl orthoformate (4.4 ml, 40.16 mmol) was added. Stirring at 70° C. was continued for another 6 hr. The reaction mixture was allowed to cool down to RT then a saturated aqueous solution of NaHCO3 was added. The product was extracted into DCM (×3) and the combined organic layers were washed with brine and dried over Na2SO4, filtered and concentrated in vacuo to give the title compound; 1H NMR (500 MHz, DMSO) δ 7.08-7.24 (3H, m), 7.50 (1H, dd, J=8.51, 1.89 Hz), 7.71 (1H, d, J=8.51 Hz), 8.37 (1H, d, J=5.52 Hz), 8.83 (1H, d, J=1.73 Hz), 9.08 (1 H, s); LC-MS (Method B): m/z=+289.9, 291.8 (M+H)+. This compound, with LC-MS purity=70%, was used in the next step without further purification.

후처리

  1. stirringStirring at 70° C.
  2. waitwas continued for another 6 hr
  3. temperatureto cool down to RT
  4. extractionThe product was extracted into DCM (×3)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-95ea796a0a154b68adcc9f65f8244992
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901313B2

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