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Dichloromethane → 5-[2-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 2386061
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HRID 2386061 반응식
[CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21](B5OC(C)(C)C(C)(C)O5)[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][C:6]([CH3:32])=[N:5]1)([CH3:3])[CH3:2].[C:33]([O:37][C:38]([N:40]1[CH2:45][C:44](OS(C(F)(F)F)(=O)=O)=[CH:43][CH2:42][CH2:41]1)=[O:39])([CH3:36])([CH3:35])[CH3:34].C(=O)([O-])[O-].[Na+].[Na+].ClCCl>COCCOC.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>[C:33]([O:37][C:38]([N:40]1[CH2:41][C:42]([C:21]2[CH:20]=[CH:19][C:16]3[C:17]4[N:18]=[C:9]([C:8]5[N:4]([CH:1]([CH3:2])[CH3:3])[N:5]=[C:6]([CH3:32])[N:7]=5)[S:10][C:11]=4[CH2:12][CH2:13][O:14][C:15]=3[CH:22]=2)=[CH:43][CH2:44][CH2:45]1)=[O:39])([CH3:36])([CH3:34])[CH3:35]
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참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 53978067tert-Butyl 3-(((trifluoromethyl)sulfonyl)oxy)-5,6-dihydropyridine-1(2H)-carboxylateHCID 582038472-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

생성물 1

HCID 58204014
5-[2-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester
수율 78.3%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매2회HCID 80711,2-Dimethoxyethane용매

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온도
80 °C

실험 절차

2-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (0.496 g, 0.00110 mol), 5-trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.550 g, 0.996 mmol) and sodium carbonate (0.317 g, 0.00299 mol) were dissolved in 1,2-dimethoxyethane (5.6 mL) and water (3.1 mL). The reaction was thoroughly degassed with N2. Tetrakis(triphenylphosphine)palladium(0) (0.115 g, 0.0000996 mol) was added and the reaction was heated to 80° C. for 3 hours. Water and dichloromethane were added and the mixture was extracted 3 times with dichloromethane. The organic layers were combined, dried with MgSO4 and concentrated. The crude was purified by flash chromatography to afford 5-[2-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as a yellow solid (396 mg). MS (ESI+) 508.2

후처리

  1. customThe reaction was thoroughly degassed with N2
  2. extractionthe mixture was extracted 3 times with dichloromethane
  3. dry with materialdried with MgSO4
  4. concentrationconcentrated
  5. customThe crude was purified by flash chromatography

출처 및 근거

ORD 기록
ord-a5cc38103ee64fc2a718258bb1895f5c
출처 데이터셋
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08263633B2

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