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4-Methyl-5-vinylthiazole → (E)-3-(2-(4-methylthiazol-5-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)-methyl)-1H-indazole-6-carbaldehyde

HRID 1615314
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HRID 1615314 반응식
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=[O:12])=[CH:8][CH:9]=2)[N:4]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:3]=1.[CH3:21][C:22]1[N:23]=[CH:24][S:25][C:26]=1[CH:27]=[CH2:28].C(N(C(C)C)C(C)C)C>CC#N.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:21][C:22]1[N:23]=[CH:24][S:25][C:26]=1/[CH:27]=[CH:28]/[C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=[O:12])=[CH:8][CH:9]=2)[N:4]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:3]=1
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참가 물질

6

반응물 3

HCID 156544-Methyl-5-vinylthiazoleHCID 81531DiisopropylethylamineHCID 581896963-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-6-carbaldehyde

생성물 1

HCID 86651974(E)-3-(2-(4-methylthiazol-5-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)-methyl)-1H-indazole-6-carbaldehyde수율 44.2%

시약·촉매·용매 2

HCID 167845
palladium(II) acetate
촉매
HCID 6342Acetonitrile용매

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온도
90 °C

실험 절차

A degassed mixture of 3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-6-carbaldehyde (70 mg, 0.17 mmol), 4-methyl-5-vinylthiazole (44 mg, 0.35 mmol), N-ethyl-N-isopropylpropan-2-amine (DIPEA, 45 mg, 0.35 mmol), Pd(OAc)2 (3.9 mg, 0.017 mmol) and P(o-MeC6H4)3 (16 mg, 0.052 mmol) in anhydrous MeCN (2 mL) were heated with stirring in a sealed tube under Ar at 90° C. for 1 d. The crude mixture was later concentrated under reduced pressure and purified by prepTLC (SiO2 5:1 hexanes/EtOAc) to provide the title compound (30 mg, 43%): 1H NMR (400 MHz, CDCl3) δ ppm 10.17 (s, 1H), 8.64 (s, 1H), 8.12 (s, 1H), 8.06 (d, J=8.28 Hz, 1H), 7.83 (d, 1H), 7.64 (d, J=16.06 Hz, 1H), 7.12 (d, J16.31 Hz, 1H), 5.82 (s, 2H), 3.62 (t, J=8.28 Hz, 2H), 2.62 (s, 3H), 0.92 (t, J=8.28 Hz, 2H), −0.05 (s, 9H); MS ESI 400.2 [M+H]+, calcd for [C20H25N3O2SSi+H]+ 400.6.

후처리

  1. temperaturewere heated
  2. concentrationThe crude mixture was later concentrated under reduced pressure
  3. custompurified by prepTLC (SiO2 5:1 hexanes/EtOAc)

출처 및 근거

ORD 기록
ord-376a62ede3a04041b4e1bcb9c84c457b
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08765748B2

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