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Potassium Carbonate → N,N-Dimethyl-5-[3-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]pyrazine-2-carboxamide

HRID 600523
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HRID 600523 반응식
[OH:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([O:18][C@H:19]2[CH2:23][CH2:22][N:21]([CH3:24])[C:20]2=[O:25])[CH:17]=1)[C:5]([NH:7][C:8]1[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=1)=[O:6].[N:26]1([C:30]([C:32]2[N:33]=[CH:34][C:35](Cl)=[N:36][CH:37]=2)=[O:31])[CH2:29]C[CH2:27]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH3:27][N:26]([CH3:29])[C:30]([C:32]1[CH:37]=[N:36][C:35]([O:1][C:2]2[CH:3]=[C:4]([C:5](=[O:6])[NH:7][C:8]3[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=3)[CH:15]=[C:16]([O:18][C@H:19]3[CH2:23][CH2:22][N:21]([CH3:24])[C:20]3=[O:25])[CH:17]=2)=[CH:34][N:33]=1)=[O:31]
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참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 46870328(Azetidin-1-yl)(5-chloropyrazin-2-yl)methanoneHCID 597611393-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide2회

생성물 1

HCID 24953713N,N-Dimethyl-5-[3-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]pyrazine-2-carboxamide수율 78%

시약·촉매·용매 1

HCID 6342
Acetonitrile
용매

실험 절차

A mixture of 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (188 mg, 0.55 mmol), 5-(azetidin-1-ylcarbonyl)-2-chloropyrazine (CAS no. 915949-00-7) (712 mg, 3.6 mmol) and potassium carbonate (152 mg, 0.55 mmol) in acetonitrile (5 mL) was stirred at 120° C. for 2 hours. The solution was evaporated to dryness then diluted with ethyl acetate (30 mL), washed with water (2×10 mL) and brine (20 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica eluting with 50-100% ethyl acetate in isohexane to afford the product (210 mg, 78%). 1H NMR δ (300 MHz, CDCL3) 2.15-2.31 (m, 1H), 2.52-2.68 (m, 1H), 2.56 (s, 3H), 2.95 (s, 3H), 3.17 (d, 6H), 3.35-3.59 (m, 2H), 4.95 (t, 1H), 7.15 (s, 1H), 7.37 (s, 1H), 7.56 (s, 1H), 8.14 (s, 1H), 8.39 (s, 1H), 8.52 (s, 2H), 9.54 (s, 1H); m/z 492 (M+H)+.

후처리

  1. customThe solution was evaporated to dryness
  2. additionthen diluted with ethyl acetate (30 mL)
  3. washwashed with water (2×10 mL) and brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe residue was purified by flash chromatography on silica eluting with 50-100% ethyl acetate in isohexane

출처 및 근거

ORD 기록
ord-fe4a74f9c0c04a4aab81ddb31fc0dc2b
출처 데이터셋
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07902200B2

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