2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 5-{2-Fluoro-4-[2-(1-methylethoxy)pyridin-3-yl]phenyl}pyrimidin-2-amine

HRID 1523930ノート

反応式

HRID 1523930 の反応式
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][C:11]([NH2:14])=[N:12][CH:13]=2)=[C:4]([F:15])[CH:3]=1.[CH:16]([O:19][C:20]1[C:25](B(O)O)=[CH:24][CH:23]=[CH:22][N:21]=1)([CH3:18])[CH3:17].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>>[F:15][C:4]1[CH:3]=[C:2]([C:25]2[C:20]([O:19][CH:16]([CH3:18])[CH3:17])=[N:21][CH:22]=[CH:23][CH:24]=2)[CH:7]=[CH:6][C:5]=1[C:8]1[CH:9]=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1

参加物

4

反応物 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 467393182-Isopropoxypyridine-3-boronic acidHCID 790224125-(4-Chloro-2-fluorophenyl)pyrimidin-2-amine

生成物 1

HCID 903127955-{2-Fluoro-4-[2-(1-methylethoxy)pyridin-3-yl]phenyl}pyrimidin-2-amine収率 49%

実験手順

To a microwave vial the following were added 5-(4-chloro-2-fluorophenyl)-pyrimidin-2-amine (50 mg, 0.22 mmol), (2-isopropoxypyridin-3-yl)boronic acid (51 mg, 0.28 mmol) and X-Phos precatalyst (4 mg, 0.005 mmol). The vial was flushed with nitrogen and then THF (0.5 mL) and 0.5 M K3PO4 (0.9 mL) were added. Both THF and the K3PO4 solution were sparged separately for 30 min prior to use. The resulting biphasic mixture was stirred at rt overnight. The reaction mixture was then poured into sat. NaHCO3 (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with water (1×50 mL) and brine (1×50 mL), dried (Na2SO4) and concentrated to dryness. The crude product was purified by HPLC to give the title compound (35 mg, 48%). MS (ESI): mass calcd. for C18H17FN4O, 324.14; m/z found, 325.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J=1.4, 2H), 8.21-8.13 (m, 1H), 7.68-7.60 (m, 1H), 7.50-7.36 (m, 3H), 6.99-6.91 (m, 1H), 5.51-5.37 (m, 1H), 5.15 (s, 2H), 1.38 (d, J=6.2, 6H).

後処理

  1. customThe vial was flushed with nitrogen
  2. additionTHF (0.5 mL) and 0.5 M K3PO4 (0.9 mL) were added
  3. customBoth THF and the K3PO4 solution were sparged separately for 30 min
  4. additionThe reaction mixture was then poured into sat. NaHCO3 (50 mL)
  5. extractionextracted with ethyl acetate (2×50 mL)
  6. washThe combined organic extracts were washed with water (1×50 mL) and brine (1×50 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated to dryness
  9. customThe crude product was purified by HPLC

出典と根拠

ORDレコード
ord-2cc50f10c8ce45af97302f3e4755262b
出典データセット
uspto-grants-2015_07
特許番号
US09079866B2

反応ノート

読み込み中…