Potassium Carbonate → (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydropyrido[2,3-b]pyrazin-1(2H)-yl)ethanone

HRID 1485775노트

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HRID 1485775 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:10]([C:11](=[O:13])[CH3:12])[C@@H:9]([CH3:14])[CH2:8][NH:7][C:6]=2[N:15]=1.[CH:16]1([N:19]2[CH:23]=[C:22](B3OC(C)(C)C(C)(C)O3)[CH:21]=[N:20]2)[CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.O1CCOCC1>[CH:16]1([N:19]2[CH:23]=[C:22]([C:2]3[CH:3]=[CH:4][C:5]4[N:10]([C:11](=[O:13])[CH3:12])[C@@H:9]([CH3:14])[CH2:8][NH:7][C:6]=4[N:15]=3)[CH:21]=[N:20]2)[CH2:18][CH2:17]1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 593271331-Cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118079164(S)-1-(6-bromo-2-methyl-3,4-dihydropyrido[2,3-b]pyrazin-1(2H)-yl)ethanone

생성물 1

HCID 118079837(S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydropyrido[2,3-b]pyrazin-1(2H)-yl)ethanone

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

A reaction vial was charged with (S)-1-(6-bromo-2-methyl-3,4-dihydropyrido[2,3-b]pyrazine-1(2H)-yl)ethanone (0.1 M solution in 1,2-dichloroethane, 0.30 mL, 0.03 mmol), 1,4-dioxane (100 μL), 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.2 M solution in 1,4-dioxane, 0.27 mL, 0.054 mmol), potassium carbonate (1.0 M solution in water, 0.090 mL, 0.090 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.02 M solution in 1,2-dichloroethane, 150 μL, 0.003 mmol). The reaction was purged with nitrogen, and heated to 80° C. on a heater shaker overnight. The reaction was diluted with ethyl acetate and washed with 1 N aqueous sodium hydroxide solution and brine. The combined organic layers were concentrated under a stream of nitrogen and vacuum to yield (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydropyrido[2,3-b]pyrazine-1(2H)-yl)ethanone. The crude product was dissolved in 1,2-dichloroethane (200 μL), and N,N-diisopropylethylamine (0.052 mL, 0.300 mmol) was added. 2-Isocyanatopropane (0.020 mL, 0.200 mmol) was then added along with a catalytic amount of DMAP (˜1 mg), and the reaction was shaken at 80° C. for 3 hours. The reaction was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution. The aqueous layer was separated and extracted with ethyl acetate and the combined organic layers were concentrated in a Genevac. The crude product was purified by mass triggered preparatory HPLC. The product-containing fractions were combined and concentrated to afford (S)-1-acetyl-6-(1-cyclopropyl-1H-pyrazol-4-yl)-N-isopropyl-2-methyl-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide. MS (ESI, pos. ion) m/z 383 [M+H]+.

후처리

  1. customA reaction
  2. customThe reaction was purged with nitrogen
  3. additionThe reaction was diluted with ethyl acetate
  4. washwashed with 1 N aqueous sodium hydroxide solution and brine
  5. concentrationThe combined organic layers were concentrated under a stream of nitrogen and vacuum

출처 및 근거

ORD 기록
ord-27d88bdea413421994c15df26ef8814b
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422281B2

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