Hydrochloric Acid → 5-(2,5-difluorobenzyl)-N-(4-(triethylsilyl)but-3-ynyl)isoxazole-3-carboxamide

HRID 58641ノート

反応式

HRID 58641 の反応式
[N:1]([CH2:4][CH2:5][C:6]#[C:7][Si:8]([CH2:13][CH3:14])([CH2:11][CH3:12])[CH2:9][CH3:10])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[F:68][C:69]1[CH:83]=[CH:82][C:81]([F:84])=[CH:80][C:70]=1[CH2:71][C:72]1[O:76][N:75]=[C:74]([C:77](O)=[O:78])[CH:73]=1>CO.O1CCOCC1.ClCCl>[F:68][C:69]1[CH:83]=[CH:82][C:81]([F:84])=[CH:80][C:70]=1[CH2:71][C:72]1[O:76][N:75]=[C:74]([C:77]([NH:1][CH2:4][CH2:5][C:6]#[C:7][Si:8]([CH2:13][CH3:14])([CH2:11][CH3:12])[CH2:9][CH3:10])=[O:78])[CH:73]=1

参加物

10

反応物 6

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668320395-(2,5-Difluorobenzyl)isoxazole-3-carboxylic acidHCID 86663839(4-Azidobut-1-ynyl)triethylsilane

生成物 1

HCID 668320895-(2,5-difluorobenzyl)-N-(4-(triethylsilyl)but-3-ynyl)isoxazole-3-carboxamide収率 47%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
60 °C

実験手順

A mixture of (4-azidobut-1-ynyl)triethylsilane (1.00; 4.78 mmol) and triphenylphosphine (1.88 g; 7.16 mmol) in methanol (10 mL) was stirred at 60° C. for two hours. HCl (4N in dioxane was added to resulting solution and the mixture was concentrated under reduced pressure. The residue was dissolved in dichloromethane. HATU (2.18 g; 5.73 mmol), N,N-diisopropylethylamine (2.06 mL; 4.78 mmol) and 5-(2,5-difluorobenzyl)isoxazole-3-carboxylic acid intermediate 74 (1.26 g; 5.25 mmol) were added and the resulting mixture was stirred at room temperature overnight and diluted in dichloromethane, washed with sodium hydrogen sulphate, sodium carbonate and brine and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 1 to 60% ethyl acetate in heptane) to yield 0.901 g (47%) of 5-(2,5-difluorobenzyl)-N-(4-(triethylsilyl)but-3-ynyl)isoxazole-3-carboxamide as a yellow oil.

後処理

  1. customto resulting solution
  2. concentrationthe mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in dichloromethane
  4. stirringthe resulting mixture was stirred at room temperature overnight
  5. washwashed with sodium hydrogen sulphate, sodium carbonate and brine
  6. concentrationconcentrated under reduced pressure
  7. customThe crude mixture was purified by flash chromatography on silica (eluent 1 to 60% ethyl acetate in heptane)

出典と根拠

ORDレコード
ord-72c4cab0fe2940d58d9d70f75ffcbb04
出典データセット
uspto-grants-2016_09
特許番号
US09434722B2

反応ノート

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