Potassium Carbonate → 5-(6-cyclopropyl-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

HRID 2046203노트

반응식

HRID 2046203 반응식
Br[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]3[N:14]=[C:15]([CH2:17][O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:16]=[C:10]3[C:9]2=[O:25])[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:32]1(B(O)O)[CH2:34][CH2:33]1>CN(C=O)C.O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:32]1([C:2]2[N:7]=[C:6]([N:8]3[CH2:13][CH2:12][N:11]4[N:14]=[C:15]([CH2:17][O:18][C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=5)[CH:16]=[C:10]4[C:9]3=[O:25])[CH:5]=[CH:4][CH:3]=2)[CH2:34][CH2:33]1

참가 물질

8

반응물 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 86670203HCID 86670203, 화합물

생성물 1

HCID 679743095-(6-cyclopropyl-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one수율 64.7%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 312751,4-Dioxane용매

반응 조건

온도
150 °C

실험 절차

Tetrakis(triphenylphosphine)palladium (0) (7 mg, 0.006 mmol), was added to a stirred suspension of 5-(6-bromo-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (50 mg, 0.12 mmol), potassium carbonate (52 mg, 0.37 mmol), cyclopropylboronic acid (21.5 mg, 0.25 mmol) in a mixture of DMF (0.5 mL) and 1,4-dioxane (0.5 mL) in a sealed tube and under nitrogen. The mixture was stirred at 150° C. for 15 minutes under microwave irradiation. The mixture was diluted with water and extracted with AcOEt. The organic layer was washed with brine, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80). The desired fractions were collected and the solvents evaporated in vacuo. The product was triturated with heptane to yield 5-(6-cyclopropyl-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (28 mg, 62% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 0.93-1.03 (m, 4H), 1.97-2.06 (m, 1H), 4.44-4.58 (m, 4H), 5.12 (s, 2H), 6.93-7.04 (m, 4H), 7.05 (s, 1H), 7.27-7.34 (m, 2H), 7.58 (t, J=7.8 Hz, 1H), 7.74-7.80 (m, 1H).

후처리

  1. extractionextracted with AcOEt
  2. washThe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvents evaporated in vacuo
  6. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 20/80)
  7. customThe desired fractions were collected
  8. customthe solvents evaporated in vacuo
  9. customThe product was triturated with heptane

출처 및 근거

ORD 기록
ord-37bf050316b5448eb2d64ccf410f99a4
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08592422B2

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