Cesium carbonate → 1-(2-Cyclopropylpyridin-4-yl)-4-fluoro-1-(2-(pyrimidin-5-yl)pyridin-4-yl)-1H-isoindol-3-amine

HRID 1662271ノート

反応式

HRID 1662271 の反応式
Br[C:2]1[CH:7]=[C:6]([C:8]2([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([CH:25]4[CH2:27][CH2:26]4)[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:4][N:3]=1.[N:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[N:30][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC.CCO.O>[CH:25]1([C:21]2[CH:20]=[C:19]([C:8]3([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([C:32]5[CH:33]=[N:28][CH:29]=[N:30][CH:31]=5)[CH:7]=4)[C:16]4[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=4)[C:10]([NH2:18])=[N:9]3)[CH:24]=[CH:23][N:22]=2)[CH2:27][CH2:26]1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 585794871-(2-Bromopyridin-4-yl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine

生成物 1

HCID 462030761-(2-Cyclopropylpyridin-4-yl)-4-fluoro-1-(2-(pyrimidin-5-yl)pyridin-4-yl)-1H-isoindol-3-amine収率 50.5%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 86587095Dimethoxyethane ethanol water溶媒

反応条件

温度
150 °C

実験手順

1-(2-Bromopyridin-4-yl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine (92 mg, 0.22 mmol), 5-pyrimidinylboronic acid (35.0 mg, 0.28 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride (8.87 mg, 10.87 μmol), cesium carbonate (0.052 mL, 0.65 mmol) and DME:EtOH:water (6:3:1) (3.00 mL) were put in a microwave vial and heated at 150° C. in a microwave reactor for 20 min. The mixture was filtered through a syringe filter and purified by prep-HPLC. The desired fractions were pooled and concentrated in vacuo. The residue was redissolved in acetonitrile and water was added. The mixture was freeze dried to give the title compound (46.9 mg, 47%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.33 (s, 2 H) 9.24 (s, 1 H) 8.67 (d, 1 H) 8.29 (d, 1 H) 7.96 (d, 1 H) 7.87 (d, 1 H) 7.58 (td, 1 H) 7.46 (dd, 1 H) 7.31 (dd, 1 H) 7.21 (d, 1 H) 7.03 (dd, 1 H) 6.79 (br. s., 2 H) 1.96-2.07 (m, 1 H) 0.80-0.96 (m, 4 H); MS (ES+) m/z 423 [M+1]+.

後処理

  1. filtrationThe mixture was filtered through a syringe
  2. filtrationfilter
  3. custompurified by prep-HPLC
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was redissolved in acetonitrile
  6. additionwater was added
  7. customdried

出典と根拠

ORDレコード
ord-b12ebb92d9a94f568f099d553007cbd9
出典データセット
uspto-grants-2011_10
特許番号
US08030500B2

反応ノート

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