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

HRID 58638노트

반응식

HRID 58638 반응식
[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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

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온도
70 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-eabffef0ccf4443ca1b4169f438369c1
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434722B2

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