Propionamide → 2-(hydroxymethyl)-N-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-6-propionamidoisonicotinamide

HRID 623634ノート

反応式

HRID 623634 の反応式
Cl[C:2]1[CH:3]=[C:4]([CH:23]=[C:24]([CH2:26][OH:27])[N:25]=1)[C:5]([NH:7][CH:8]([C:10]1[CH:11]=[N:12][C:13]([O:17][CH2:18][C:19]([F:22])([F:21])[F:20])=[C:14]([CH3:16])[CH:15]=1)[CH3:9])=[O:6].[C:28]([NH2:32])(=[O:31])[CH2:29][CH3:30].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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].O1CCOCC1>[OH:27][CH2:26][C:24]1[CH:23]=[C:4]([CH:3]=[C:2]([NH:32][C:28](=[O:31])[CH2:29][CH3:30])[N:25]=1)[C:5]([NH:7][CH:8]([C:10]1[CH:11]=[N:12][C:13]([O:17][CH2:18][C:19]([F:22])([F:21])[F:20])=[C:14]([CH3:16])[CH:15]=1)[CH3:9])=[O:6]

参加物

7

反応物 4

HCID 6578PropionamideHCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 874274592-chloro-6-(hydroxymethyl)-N-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)isonicotinamide

生成物 1

HCID 675089232-(hydroxymethyl)-N-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-6-propionamidoisonicotinamide収率 25%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

A mixture of 2-chloro-6-(hydroxymethyl)-N-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)isonicotinamide (17 mg, 0.04 mmol, Step-3, single enantiomer), propionamide (6 mg, 0.08 mmol), tris(dibenzylideneacetone)dipalladium(0) (1 mg, 0.8 microM), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (1.5 mg, 2.5 microM), tripotassium phosphate (11 mg, 0.05 mmol) and 1,4-dioxane (1 mL) is heated by microwave irradiation at 150° C. for 1 hour. After cooling to room temperature, the mixture is filtered through a pad of celite. The filtrate is concentrated under reduced pressure and the residue is diluted with methanol (4 mL) and applied onto a strong cation exchange cartridge (BondElute(registered trademark) SCX, 1 g/6 mL, Varian Inc.), and the solid phase matrix is rinsed with methanol (5 mL). The crude mixture is eluted with 1M ammonia in methanol (5 mL) and concentrated under reduced pressure and then by preparative LC-MS to give 4.4 mg (24% yield) of the title compound.

後処理

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture is filtered through a pad of celite
  3. concentrationThe filtrate is concentrated under reduced pressure
  4. additionthe residue is diluted with methanol (4 mL)
  5. wash), and the solid phase matrix is rinsed with methanol (5 mL)
  6. washThe crude mixture is eluted with 1M ammonia in methanol (5 mL)
  7. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-99d3da0c434b495d998b05ce4d175db6
出典データセット
uspto-grants-2016_04
特許番号
US09302991B2

反応ノート

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