Carbonic acid, bis(1,1-dimethylethyl) ester → HCID 67389163, compound

HRID 908478Notes

Reaction equation

HRID 908478 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[O:10][C:11]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:12]=3[N:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.[C:19](=[O:30])([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])OC(C)(C)C>CN(C)C1C=CN=CC=1.CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[O:10][C:11]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:12]=3[N:13]=2)[C:5]([N:8]([C:19]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:30])[C:19](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 10219638Carbonic acid, bis(1,1-dimethylethyl) esterHCID 67388682HCID 67388682, compound

Product 1

HCID 67389163HCID 67389163, compoundYield 89.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

N,N-dimethylpyridin-4-amine (0.190 g), was added to a stirred suspension of 5-bromo-3-(4-fluoro-1,3-benzoxazol-2-yl)pyridin-2-amine (2.4 g) and di-tert-butyl carbonate (4.83 g) in DMF (50 ml) at 25° C. under nitrogen. The resulting suspension was stirred at 25° C. for 45 hours. The DMF was evaporated under reduce pressure. The mixture was adsorbed on silica gel. The crude product was purified by flash chromatography on silica gel eluting with 0 to 2% methanol in dichloromethane. The solvent was evaporated to dryness to afford tert-butyl N-[5-bromo-3-(4-fluoro-1,3-benzoxazol-2-yl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate (3.54 g, 89%) as a pale orange solid. NMR Spectrum: (CDCl3) 1.36 (s, 18H), 7.12 (dd, 1H), 7.38 (ddd, 1H), 7.42 (d, 1H), 8.72 (d, 1H), 8.85 (d, 1H); Mass spectrum: M+H+ 508-510 PdCl2dppf (0.278 g), potassium acetate (2.095 ml) and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (1.923 g) were added over a period of 10 minutes, to a stirred solution tert-butyl N-[5-bromo-3-(4-fluoro-1,3-benzoxazol-2-yl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate (3.5 g) dissolved in dioxane (30 ml) degazed and under argon. The resulting mixture was stirred at 80° C. for 3 hours. The salts were filtered; The mixture was evaporated under reduce pressure. The crude product was purified by flash chromatography on silica gel eluting with 30 to 40% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl N-tert-butoxycarbonyl-N-[3-(4-fluoro-1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (3.26 g) as a pale orange solid. NMR Spectrum: (CDCl3) 1.33 (s, 18H), 1.39 (s, 12H), 7.10 (dd, 1H), 7.34 (ddd, 1H), 7.42 (d, 1H), 8.99 (d, 1H), 9.08 (d, 1H); Mass spectrum: M-(boc+pinacol)+H+ 374

Workup

  1. customThe DMF was evaporated
  2. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 2% methanol in dichloromethane
  3. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-d411d6a547274bae84c2fd99b9189409
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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