Diisopropylethylamine → Netupitant

HRID 1477269노트

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HRID 1477269 반응식
[CH3:1][NH:2][C:3]1[CH:4]=[N:5][C:6]([N:16]2[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]2)=[CH:7][C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH3:15].C(N(C(C)C)C(C)C)C.[F:32][C:33]([F:51])([F:50])[C:34]1[CH:35]=[C:36]([C:44]([CH3:49])([CH3:48])[C:45](Cl)=[O:46])[CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1.C(=O)(O)[O-].[Na+]>ClCCl>[F:32][C:33]([F:51])([F:50])[C:34]1[CH:35]=[C:36]([C:44]([CH3:49])([CH3:48])[C:45]([N:2]([CH3:1])[C:3]2[CH:4]=[N:5][C:6]([N:16]3[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]3)=[CH:7][C:8]=2[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[CH3:15])=[O:46])[CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 112671412-(3,5-Bis(trifluoromethyl)phenyl)-2-methylpropanoyl chlorideHCID 158874123-Pyridinamine, N-methyl-4-(2-methylphenyl)-6-(4-methyl-1-piperazinyl)-

생성물 1

HCID 6451149Netupitant수율 81%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
37.5 °C

실험 절차

A solution of 20 g (67.5 mmol) methyl-[6-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyridin-3-yl]-amine and 17.5 ml (101 mmol) N-ethyldiisopropylamine in 200 ml dichloromethane was cooled in an ice bath and a solution of 24 g (75 mmol)2-(3,5-bis-trifluoromethyl-phenyl)-2-methyl-propionyl chloride in 50 ml dichloromethane was added dropwise. The reaction mixture was warmed to 35-40° C. for 3 h, cooled to room temperature again and was stirred with 250 ml saturated sodium bicarbonate solution. The organic layer was separated and the aqueous phase was extracted with dichloromethane. The combined organic layers were dried (magnesium sulfate) and evaporated. The residue was purified by flash chromatography to give 31.6 g (81%) of 2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethyl-N-(6-(4-methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-yl)propanamide as white crystals.

후처리

  1. temperaturecooled to room temperature again
  2. customThe organic layer was separated
  3. extractionthe aqueous phase was extracted with dichloromethane
  4. dry with materialThe combined organic layers were dried (magnesium sulfate)
  5. customevaporated
  6. customThe residue was purified by flash chromatography

출처 및 근거

ORD 기록
ord-06d124e346a5448881dfad7ace4bcdaa
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09403772B2

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