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2-(Trimethylstannyl)isonicotinonitrile → 2-(3-(3-Amino-4-fluoro-1-(2-methoxypyridin-4-yl)-1H-isoindol-1-yl) phenyl)isonicotinonitrile

HRID 1662259
ノート
印刷プレビュー

反応式

HRID 1662259 の反応式
Br[C:2]1[CH:3]=[C:4]([C:8]2([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([O:25][CH3:26])[CH:20]=3)[C:16]3[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=3)[C:10]([NH2:18])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.C[Sn](C)(C)[C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][N:36]=1)[C:32]#[N:33]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[NH2:18][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])[C:8]([C:4]2[CH:3]=[C:2]([C:29]3[CH:30]=[C:31]([CH:34]=[CH:35][N:36]=3)[C:32]#[N:33])[CH:7]=[CH:6][CH:5]=2)([C:19]2[CH:24]=[CH:23][N:22]=[C:21]([O:25][CH3:26])[CH:20]=2)[N:9]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 2

HCID 585794962-(Trimethylstannyl)isonicotinonitrileHCID 585794981-(3-Bromophenyl)-4-fluoro-1-(2-methoxypyridin-4-yl)-1H-isoindol-3-amine

生成物 1

HCID 462024142-(3-(3-Amino-4-fluoro-1-(2-methoxypyridin-4-yl)-1H-isoindol-1-yl) phenyl)isonicotinonitrile収率 9%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒
HCID 6228
Dimethylformamide
溶媒

反応条件

温度
110 °C

実験手順

1-(3-Bromophenyl)-4-fluoro-1-(2-methoxypyridin-4-yl)-1H-isoindol-3-amine (0.200 g, 0.49 mmol), 2-(trimethylstannyl)isonicotinonitrile (0.194 g, 0.73 mmol), tetrakis(triphenylphosphine)palladium(0) (0.056 g, 0.05 mmol) and DMF (4 mL) were put in a microwave vial and heated in a microwave reactor at 110° C. for 20 min, then at 150° C. for 20 min. The reaction mixture was filtered through a syringe filter and purified by preparative HPLC. The desired fractions were pooled and concentrated in vacuo. The residue was partitioned between aqueous sodium bicarbonate (sat.) and ethyl acetate. The aqueous layer was extracted with EtOAc (×2), the combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound (0.018 g, 9%). 1H NMR (500 MHz, DMSO-d6) δ ppm 8.86 (dd, 1 H) 8.40 (t, 1 H) 8.11-8.15 (m, 1 H) 8.04 (d, 1 H) 8.01 (ddd, 1 H) 7.78-7.81 (m, 1 H) 7.66 (d, 1 H) 7.51-7.57 (m, 1 H) 7.42-7.47 (m, 2 H) 7.24-7.31 (m, 1 H) 6.88 (dd, 1 H) 6.59-6.71 (m, 3 H) 3.79 (s, 3 H); MS (ES+) m/z 436 [M+H]+.

後処理

  1. filtrationThe reaction mixture was filtered through a syringe
  2. filtrationfilter
  3. custompurified by preparative HPLC
  4. concentrationconcentrated in vacuo
  5. customThe residue was partitioned between aqueous sodium bicarbonate (sat.) and ethyl acetate
  6. extractionThe aqueous layer was extracted with EtOAc (×2)
  7. dry with materialthe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-1a581cc2e576405a9ae77887557a1306
出典データセット
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08030500B2

反応ノート

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