Potassium Phosphate, Tribasic → Tert-butyl 3-((2'-fluoro-6-methoxy-[3,4'-bipyridin]-5-yl)amino)azetidine-1-carboxylate

HRID 2283467ノート

反応式

HRID 2283467 の反応式
Cl[C:2]1[CH:3]=[C:4]([NH:10][CH:11]2[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[F:22][C:23]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[CH:25][N:24]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[F:22][C:23]1[CH:28]=[C:27]([C:2]2[CH:7]=[N:6][C:5]([O:8][CH3:9])=[C:4]([NH:10][CH:11]3[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]3)[CH:3]=2)[CH:26]=[CH:25][N:24]=1

参加物

5

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 120601642-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 118251077Tert-butyl 3-((5-chloro-2-methoxypyridin-3-yl)amino)azetidine-1-carboxylate

生成物 1

HCID 118251462Tert-butyl 3-((2'-fluoro-6-methoxy-[3,4'-bipyridin]-5-yl)amino)azetidine-1-carboxylate収率 100.6%

試薬・触媒・溶媒 1

HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
100 °C

実験手順

To a solution of tert-butyl 3-((5-chloro-2-methoxypyridin-3-yl)amino)azetidine-1-carboxylate (2.00 g, 6.37 mmol) in dioxane/water (5:1, 38 mL) was added 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1.85 g 8.29 mmol), Xphos-Pd-G2 (125 mg, 0.159 mmol), and K3PO4 (2.90 g, 13.7 mmol). The reaction mixture was stirred at 100° C. under nitrogen for 1 h. After cooling to RT, the reaction mixture was filtered and washed with ethyl acetate (100 mL). The organic layer was washed with water (60 mL), brine (60 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to obtain 2.4 g of tert-butyl 3-((2′-fluoro-6-methoxy-[3,4′-bipyridin]-5-yl)amino)azetidine-1-carboxylate as a white yellow solid (100%): 1H NMR (400 MHz, CDCl3) δ 8.17 (d, J=5.3 Hz, 1H), 7.75 (d, J=2.2 Hz, 1H), 7.24 (dt, J=5.5, 1.6 Hz, 1H), 6.96 (t, J=1.5 Hz, 1H), 6.58 (d, J=2.1 Hz, 1H), 4.60 (d, J=6.5 Hz, 1H), 4.29 (dd, J=8.9, 7.1 Hz, 2H), 4.19 (qd, J=6.7, 5.7, 1.9 Hz, 1H), 3.99 (s, 3H), 3.75 (dd, J=9.1, 4.7 Hz, 2H), 1.38 (s, 9H); MS (ES) m/z 375 (M+H).

後処理

  1. temperatureAfter cooling to RT
  2. filtrationthe reaction mixture was filtered
  3. washwashed with ethyl acetate (100 mL)
  4. washThe organic layer was washed with water (60 mL), brine (60 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography

出典と根拠

ORDレコード
ord-462c6f30e46d4f3280fc6fe3c89ceb9f
出典データセット
uspto-grants-2015_09
特許番号
US09145393B2

反応ノート

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