Cesium carbonate → 6-chloro-4-(5-(4-hydroxy-4-methylpiperidin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one

HRID 1431193노트

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HRID 1431193 반응식
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[N:5]=[C:6]([Cl:8])[CH:7]=1.[NH2:11][C:12]1[N:17]=[CH:16][C:15]([N:18]2[CH2:23][CH2:22][C:21]([CH3:25])([OH:24])[CH2:20][CH2:19]2)=[CH:14][CH:13]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:8][C:6]1[CH:7]=[C:2]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([N:18]3[CH2:23][CH2:22][C:21]([OH:24])([CH3:25])[CH2:20][CH2:19]3)=[CH:16][N:17]=2)[C:3](=[O:10])[N:4]([CH3:9])[N:5]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-oneHCID 667426091-(6-Aminopyridin-3-yl)-4-methylpiperidin-4-ol

생성물 1

HCID 667429326-chloro-4-(5-(4-hydroxy-4-methylpiperidin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one수율 62.9%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

A solution of 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (902 mg, 4.04 mmol), 1-(6-aminopyridin-3-yl)-4-methylpiperidin-4-ol (761 mg, 3.67 mmol), Xantphos (159 mg, 275 μmol) and cesium carbonate (3.59 g, 11 mmol) in dry dioxane (10 ml) was vacuum de-gassed and placed under an argon atmosphere. To this mixture was added tris(dibenzylideneacetone)dipalladium (0) (38 mg, 36.7 μmol) and the vacuum de-gas cycle was repeated. The material was heated at 90° C. (oil bath) with vigorous stirring overnight. The flask was cooled to ambient and the contents were filtered through a plug of celite, rinsing well with dioxane, and concentrating. The product was purified by preparative HPLC on silica gel, using a gradient of 5% to 70% ethylacetate/hexane. This provided the desired product as a light yellow solid (807 mg 62.9%). (M+H)+=350, 352 m/e.

후처리

  1. customde-gassed
  2. customthe vacuum de-gas cycle
  3. temperatureThe flask was cooled to ambient and the contents
  4. filtrationwere filtered through a plug of celite
  5. washrinsing well with dioxane
  6. concentrationconcentrating
  7. customThe product was purified by preparative HPLC on silica gel

출처 및 근거

ORD 기록
ord-1502f00ff2a04d6aa16bcac79bb7a468
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940741B2

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