Triphenylphosphine → N-(2-(5-cyano-2-(triethylsilyl)-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide

HRID 1918627ノート

反応式

HRID 1918627 の反応式
[N:1]([CH2:4][CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]#[N:16])[CH:13]=2)[NH:8][C:7]=1[Si:17]([CH2:22][CH3:23])([CH2:20][CH3:21])[CH2:18][CH3:19])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.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:76][C:77]1[CH:91]=[CH:90][C:89]([F:92])=[CH:88][C:78]=1[CH2:79][C:80]1[O:84][N:83]=[C:82]([C:85](O)=[O:86])[CH:81]=1>CO.CN(C=O)C>[C:15]([C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([Si:17]([CH2:22][CH3:23])([CH2:20][CH3:21])[CH2:18][CH3:19])=[C:6]2[CH2:5][CH2:4][NH:1][C:85]([C:82]1[CH:81]=[C:80]([CH2:79][C:78]2[CH:88]=[C:89]([F:92])[CH:90]=[CH:91][C:77]=2[F:76])[O:84][N:83]=1)=[O:86])#[N:16]

参加物

8

反応物 5

HCID 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 866638383-(2-azidoethyl)-2-(triethylsilyl)-1H-indole-5-carbonitrile

生成物 1

HCID 66832142N-(2-(5-cyano-2-(triethylsilyl)-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide収率 48%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

A mixture of 3-(2-azidoethyl)-2-(triethylsilyl)-1H-indole-5-carbonitrile (0.400 g; 1.23 mmol) and triphenylphosphine (0.523 g; 2.00 mmol) in methanol (10 mL) was stirred at 70° C. for 2 hours. The reaction mixture was concentrated under reduced pressure and the crude material was dissolved in a mixture of 5-(2,5-difluorobenzyl)isoxazole-3-carboxylic acid intermediate 74 (0.318 g, 1.33 mmol), HATU (0.506 g; 1.33 mmol) and N,N diisopropylethylamine (0.614 mL; 3.33 mmol) in DMF (10 mL), was stirred at room temperature for 72 hours. The reaction mixture was partitioned between ethyl acetate and sodium hydrogen sulphate; the organic layer was washed with sodium carbonate, brine, dried and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica (eluent 2 to 60% ethyl acetate in heptane) to yield 0.338 g (48%) of N-(2-(5-cyano-2-(triethylsilyl)-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)isoxazole-3-carboxamide as a solid.

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. stirringwas stirred at room temperature for 72 hours
  3. customThe reaction mixture was partitioned between ethyl acetate and sodium hydrogen sulphate
  4. washthe organic layer was washed with sodium carbonate, brine
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. customThe crude mixture was purified by flash chromatography on silica (eluent 2 to 60% ethyl acetate in heptane)

出典と根拠

ORDレコード
ord-4f14b34901aa4b3eb9ab1cc5d46777bf
出典データセット
uspto-grants-2013_12
特許番号
US08618138B2

反応ノート

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