Diisopropylethylamine → (E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)-N-((tetrahydro-2H-pyran-2-yl)oxy)acrylamide

HRID 632635ノート

反応式

HRID 632635 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[C:14]([O:17][CH3:18])[CH:15]=[CH:16][C:10]=3[C:9]=2[O:19][C:20]2[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28](O)=[O:29])=[CH:22][CH:21]=2)=[C:4]([CH3:31])[CH:3]=1.[O:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH:33]1[O:38][NH2:39].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[C:14]([O:17][CH3:18])[CH:15]=[CH:16][C:10]=3[C:9]=2[O:19][C:20]2[CH:21]=[CH:22][C:23](/[CH:26]=[CH:27]/[C:28]([NH:39][O:38][CH:33]3[CH2:34][CH2:35][CH2:36][CH2:37][O:32]3)=[O:29])=[CH:24][CH:25]=2)=[C:4]([CH3:31])[CH:3]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86730646(E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

生成物 1

HCID 86730650(E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)-N-((tetrahydro-2H-pyran-2-yl)oxy)acrylamide収率 86.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a 30 mL screw cap vial, (E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (50 mg, 0.115 mmol) was dissolved in DMF (2 mL). The vial was charged with O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (27.0 mg, 0.230 mmol), HATU (65.6 mg, 0.173 mmol), and DIEA (0.060 mL, 0.345 mmol). The reaction mixture was stirred for 30 min at room temperature. The reaction was quenched with sat. NH4Cl and diluted with DCM. The organic phase was collected (phase separator) and concentrated by vacuum to afford to crude product. The crude material was purified by column chromatography (SiO2, 1-80% Heptanes/EtOAc) to afford (E)-3-(4-((2-(4-fluoro-2-methylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)-N-((tetrahydro-2H-pyran-2-yl)oxy)acrylamide (53 mg, 0.099 mmol, 86% yield). 1H NMR (400 MHz, CD3OD) δ ppm=1.48-1.73 (m, 3 H), 1.73-1.96 (m, 3 H), 2.36 (s, 3 H), 3.56-3.70 (m, 1 H), 3.89 (s, 3 H), 3.98-4.14 (m, 1 H), 4.96 (br. s., 1H), 6.35 (d, J=15.66 Hz, 1 H), 6.79-6.95 (m, 3 H), 6.95-7.07 (m, 2 H), 7.26-7.39 (m, 2 H), 7.39-7.48 (m, 3 H), 7.52 (d, J=16.17 Hz, 1 H), LC/MS (m/z, MH+): 534.1.

後処理

  1. customTo a 30 mL screw cap vial
  2. customThe reaction was quenched with sat. NH4Cl
  3. additiondiluted with DCM
  4. customThe organic phase was collected (phase separator)
  5. concentrationconcentrated by vacuum
  6. customto afford to crude product
  7. customThe crude material was purified by column chromatography (SiO2, 1-80% Heptanes/EtOAc)

出典と根拠

ORDレコード
ord-6169a5240be84c5381c839ea8ded048f
出典データセット
uspto-grants-2016_04
特許番号
US09321746B2

反応ノート

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