Nitrogen → methyl 5-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}-2-furoate

HRID 1508564Notes

Reaction equation

HRID 1508564 reaction equation
[N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])[C:8]([C:33]3[CH:38]=[C:37](I)[CH:36]=[CH:35][C:34]=3[O:40][CH3:41])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[CH3:42][O:43][C:44]([C:46]1[O:50][C:49](B(O)O)=[CH:48][CH:47]=1)=[O:45].N#N.C([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])[C:8]([C:33]3[CH:38]=[C:37]([C:49]4[O:50][C:46]([C:44]([O:43][CH3:42])=[O:45])=[CH:47][CH:48]=4)[CH:36]=[CH:35][C:34]=3[O:40][CH3:41])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 12163655(5-(Methoxycarbonyl)furan-2-YL)boronic acidHCID 86704603(4S,5R)-3-{[6-azetidin-1-yl-3-(5-iodo-2-methoxyphenyl)pyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 56970474methyl 5-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}-2-furoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of (4S,5R)-3-{[6-azetidin-1-yl-3-(5-iodo-2-methoxyphenyl)pyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (20 mg, 0.029 mmol) and [5-(methoxycarbonyl)-2-furyl]boronic acid (14.75 mg, 0.087 mmol) in THF (0.5 mL) was degassed with N2 at 25° C. 1N K2CO3 (0.5 mL) was added followed by 1,1-bis(di-tert-butylphosphino)ferrocene palladium dichloride (1.885 mg, 2.89 μmol) and the reaction was stirred vigorously at 25° C. under N2 overnight. The reaction was diluted with water and extracted with EtOAc (3×). The combined extracts were dried (Na2SO4) and concentrated in vacuo to afford the crude product. This was purified by preparative TLC (20×20, 1000 μm, hexanes/EtOAc (70/30)) to give methyl 5-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}-2-furoate. LCMS calc.=689.2. found=690.2 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.85 (s, 1H); 7.81-7.55 (m, 4H); 7.37 (d, J=8.3 Hz, 1H); 7.24 (d, J=3.7 Hz, 1H); 7.02 (d, J=8.6 Hz, 1H); 6.66 (s, 1H); 6.31 (d, J=8.3 Hz, 1H); 5.74-5.36 (m, 1H); 4.84 (d, J=16.1 Hz, 1H); 4.25 (s, 1H); 4.18-4.01 (m, 5H); 3.90 (s, 3H); 3.87 (s, 3H); 2.48-2.39 (m, 2H); 0.75-0.59 (m, 1H).

Workup

  1. extractionextracted with EtOAc (3×)
  2. dry with materialThe combined extracts were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customto afford the crude product
  5. customThis was purified by preparative TLC (20×20, 1000 μm, hexanes/EtOAc (70/30))

Sources & evidence

ORD record
ord-878a7b979c3448079e0ee1c3ebd98c44
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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