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

HRID 2283467Notes

Reaction equation

HRID 2283467 reaction equation
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

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

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

Conditions

Temperature
100 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-462c6f30e46d4f3280fc6fe3c89ceb9f
Source dataset
uspto-grants-2015_09
Patent number
US09145393B2

Reaction notes

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