Lithium Chloride → 13-(1-Ethoxyethenyl)-12-fluoro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene

HRID 1530701노트

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HRID 1530701 반응식
Br[C:2]1[CH:15]=[C:14]2[C:5]([O:6][CH2:7][CH2:8][N:9]3[C:13]2=[N:12][C:11]([C:16]2[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[C:18]([CH3:24])[N:17]=2)=[CH:10]3)=[CH:4][C:3]=1[F:25].[Li+].[Cl-].C([Sn](CCCC)(CCCC)[C:33]([O:35][CH2:36][CH3:37])=[CH2:34])CCC.[F-].[K+]>C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:36]([O:35][C:33]([C:2]1[CH:15]=[C:14]2[C:5]([O:6][CH2:7][CH2:8][N:9]3[C:13]2=[N:12][C:11]([C:16]2[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[C:18]([CH3:24])[N:17]=2)=[CH:10]3)=[CH:4][C:3]=1[F:25])=[CH2:34])[CH3:37]

참가 물질

7

반응물 4

HCID 433294Lithium ChlorideHCID 522689Potassium FluorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 6831287410-Bromo-9-fluoro-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

생성물 1

HCID 6831301413-(1-Ethoxyethenyl)-12-fluoro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene수율 100.5%

시약·촉매·용매 2

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 8028Tetrahydrofuran용매2회

실험 절차

To a suspension of 13-bromo-12-fluoro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene (2.00 g, 4.93 mmol) and LiCl (620 mg, 14.8 mmol) in dry THF (15 mL), was added tri-n-butyl(1-ethoxyvinyl)tin (1.78 g, 4.93 mmol) and tetrakis(triphenylphosphine) palladium (185 mg, 0.160 mmol) under nitrogen at room temperature. The resultant mixture was heated under 80° C. for 24 h in a seal tube. After cooling down, the mixture was diluted with THF, treated with an aqueous 0.16 M potassium fluoride solution (20 ml), and stirred at ambient temperature for 1 h. The precipitated tri-nbutylstannyl fluoride was removed by filtration. The filtrate was evaporated under reduced pressure to give an aqueous suspension, which was extracted with ethyl acetate. The combined organic layers were washed with water and evaporated in vacuo to give the crude product (1.97 g, over 100% yield) a yellow solid, which was used directly in the next step without further purification. LCMS m/z [M+H]+ 398.1

후처리

  1. temperatureAfter cooling down
  2. customThe precipitated tri-nbutylstannyl fluoride was removed by filtration
  3. customThe filtrate was evaporated under reduced pressure
  4. customto give an aqueous suspension, which
  5. extractionwas extracted with ethyl acetate
  6. washThe combined organic layers were washed with water
  7. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-f05b9f11aeb248ad89e54cd36f4acd81
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090628B2

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