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

HRID 2283467노트

반응식

HRID 2283467 반응식
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

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

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

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-462c6f30e46d4f3280fc6fe3c89ceb9f
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09145393B2

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