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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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Water → 1,1-Dimethylethyl (3R)-3-({[7-(1-ethyl-1H-pyrazol-4-yl)-1,6-naphthyridin-5-yl]amino}methyl)-3-fluoro-1-piperidinecarboxylate

HRID 473320
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HRID 473320 반응식
C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:7]([N:9]1[CH:13]=[C:12](B2OC(C)(C)C(C)(C)O2)[CH:11]=[N:10]1)[CH3:8].Cl[C:24]1[CH:33]=[C:32]2[C:27]([CH:28]=[CH:29][CH:30]=[N:31]2)=[C:26]([NH:34][CH2:35][C@:36]2([F:49])[CH2:41][CH2:40][CH2:39][N:38]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:37]2)[N:25]=1.O>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]>[CH2:7]([N:9]1[CH:13]=[C:12]([C:24]2[CH:33]=[C:32]3[C:27]([CH:28]=[CH:29][CH:30]=[N:31]3)=[C:26]([NH:34][CH2:35][C@:36]3([F:49])[CH2:41][CH2:40][CH2:39][N:38]([C:42]([O:44][C:45]([CH3:47])([CH3:46])[CH3:48])=[O:43])[CH2:37]3)[N:25]=2)[CH:11]=[N:10]1)[CH3:8]
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참가 물질

7

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 113790451-Ethyl-1H-pyrazole-4-boronic acid, pinacol esterHCID 866768011,1-Dimethylethyl (3R)-3-{[(7-chloro-1,6-naphthyridin-5-yl)amino]methyl}-3-fluoro-1-piperidinecarboxylate

생성물 1

HCID 682099441,1-Dimethylethyl (3R)-3-({[7-(1-ethyl-1H-pyrazol-4-yl)-1,6-naphthyridin-5-yl]amino}methyl)-3-fluoro-1-piperidinecarboxylate

시약·촉매·용매 2

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

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온도
150 °C

실험 절차

To a 2-5 mL microwave vial under nitrogen was added caesium carbonate (990 mg, 3.04 mmol) and 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (292 mg, 1.317 mmol) (Boron Molecular). 1,1-Dimethylethyl (3R)-3-{[(7-chloro-1,6-naphthyridin-5-yl)amino]methyl}-3-fluoro-1-piperidinecarboxylate (400 mg, 1.013 mmol) was dissolved in 1,4-dioxane (4 ml) and water (0.8 ml) and added in one aliquot. Nitrogen was bubbled through the resultant suspension for ˜2 min. Tetrakis(triphenylphosphine)palladium (0) (117 mg, 0.101 mmol) was then added in one portion and nitrogen bubbled through the yellow suspension for a further ˜1 min. The microwave vial was sealed and heated at 150° C. in a microwave reactor for 1 h. LCMS showed the reaction had gone to completion. The reaction was partitioned between water (20 ml) and ethyl acetate (20 ml). The aqueous layer was further extracted with ethyl acetate (2×20 ml) and the combined organics washed with brine (10 ml). The organics were dried (Na2SO4) and concentrated in vacuo.

후처리

  1. customNitrogen was bubbled through the resultant suspension for ˜2 min
  2. custombubbled through the yellow suspension for a further ˜1 min
  3. customThe microwave vial was sealed
  4. customThe reaction was partitioned between water (20 ml) and ethyl acetate (20 ml)
  5. extractionThe aqueous layer was further extracted with ethyl acetate (2×20 ml)
  6. washthe combined organics washed with brine (10 ml)
  7. dry with materialThe organics were dried (Na2SO4)
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-4e1d425754844e8a896a2d77e601e9e8
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08633319B2

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