Acetic Acid → 6-Bromo-2-(2-cyclopropyl-4-pyrimidinyl)-1h-imidazo[4,5-b]pyrazine

HRID 931231노트

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HRID 931231 반응식
[Br:1][C:2]1[N:3]=[C:4]([NH2:9])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH:10]1([C:13]2[N:18]=[C:17]([C:19](=N)OCC)[CH:16]=[CH:15][N:14]=2)[CH2:12][CH2:11]1.C(N(CC)CC)C.C(O)(=O)C>C(O)C>[Br:1][C:2]1[N:3]=[C:4]2[NH:9][C:19]([C:17]3[CH:16]=[CH:15][N:14]=[C:13]([CH:10]4[CH2:12][CH2:11]4)[N:18]=3)=[N:8][C:5]2=[N:6][CH:7]=1

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 27718575-Bromopyrazine-2,3-diamineHCID 89854162Ethyl 2-cyclopropylpyrimidine-4-carbimidate2회

생성물 1

HCID 898533786-Bromo-2-(2-cyclopropyl-4-pyrimidinyl)-1h-imidazo[4,5-b]pyrazine수율 25%

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
100 °C

실험 절차

A mixture of 5-bromopyrazine-2,3-diamine (50 mg, 0.3 mmol) and ethyl 2-cyclopropylpyrimidine-4-carbimidate (Intermediate 19, 50.7 mg, 0.3 mmol), triethylamine (73.8 μL, 0.5 mmol), acetic acid (244 μL, 4.2 mmol) and ethanol (0.8 mL) was heated to 100° C. for 30 min. The mixture was concentrated and diluted with water. Then a saturated aqueous solution of sodium bicarbonate was added and the mixture was extracted with ethyl acetate. The organics were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The crude material was purified via flash chromatography (0-5% methanol in dichloromethane) to afford 6-bromo-2-(2-cyclopropylpyrimidin-4-yl)-1H-imidazo[4,5-b]pyrazine (21 mg, 25%).

후처리

  1. concentrationThe mixture was concentrated
  2. additiondiluted with water
  3. additionThen a saturated aqueous solution of sodium bicarbonate was added
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified via flash chromatography (0-5% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-9bc4a801e7794d64b45e16619e18ba17
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296745B2

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