Potassium Carbonate → N-[((5S)-3-{3-Fluoro-4-[5-({[(6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl]oxy}methyl)-2-thienyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide

HRID 1446082Notes

Reaction equation

HRID 1446082 reaction equation
Br[C:2]1[S:6][C:5]([CH2:7][O:8][C@@H:9]2[CH2:14][O:13][C:12]3=[N:15][C:16]([N+:18]([O-:20])=[O:19])=[CH:17][N:11]3[CH2:10]2)=[CH:4][CH:3]=1.[F:21][C:22]1[CH:23]=[C:24]([N:37]2[CH2:41][C@H:40]([CH2:42][NH:43][C:44](=[O:46])[CH3:45])[O:39][C:38]2=[O:47])[CH:25]=[CH:26][C:27]=1B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[K+].[K+]>CCO.C1(C)C=CC=CC=1.CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:21][C:22]1[CH:23]=[C:24]([N:37]2[CH2:41][C@H:40]([CH2:42][NH:43][C:44](=[O:46])[CH3:45])[O:39][C:38]2=[O:47])[CH:25]=[CH:26][C:27]=1[C:2]1[S:6][C:5]([CH2:7][O:8][C@@H:9]2[CH2:14][O:13][C:12]3=[N:15][C:16]([N+:18]([O-:20])=[O:19])=[CH:17][N:11]3[CH2:10]2)=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 10407282(S)-N-((3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamideHCID 44818300(6S)-6-[(5-Bromo-2-thienyl)methoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine

Product 1

HCID 44241802N-[((5S)-3-{3-Fluoro-4-[5-({[(6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl]oxy}methyl)-2-thienyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamideYield 48.1%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (6S)-6-[(5-bromo-2-thienyl)methoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (0.200 g, 0.555 mmol) and N-({(5S)-3-[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide (0.252 g, 0.666 mmol) in EtOH (3 mL), toluene (5 mL), DMF (8 mL) and K2CO3 (2 mL, 2 M, 4 mmol) was purged with nitrogen. PdCl2(dppf) (23 mg, 0.03 mmol) was added and the mixture was refluxed under nitrogen for 1 h then partitioned between EtOAc and water. Column chromatography (9:1 DCM/MeOH) gave a solid which was then reprecipitated from DCM/MeOH to give the titled compound (0.142 g, 48%) as a pale grey solid. APCI MS m/z 532 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 8.21 (t, J=5.7 Hz, 1H), 8.02 (s, 1H), 7.76 (t, J=8.9 Hz, 1H), 7.59 (dd, J=14.0, 2.1 Hz, 1H), 7.36-7.43 (m, 2H), 7.13 (d, J=3.3, 1H), 4.87 (d, J=13.6 Hz, 1H), 4.84 (d, J=13.6 Hz, 1H), 4.72-4.80 (m, 1H), 4.64 (bd, J=12.4 Hz, 1H), 4.47 (d, J=11.9 Hz, 1H), 4.21-4.30 (m, 3H), 4.15 (t, J=9.1 Hz, 1H), 3.74-3.81 (m, 1H), 3.43 (t, J=5.4 Hz, 2H), 1.84 (s, 3H).

Workup

  1. customwas purged with nitrogen
  2. temperaturethe mixture was refluxed under nitrogen for 1 h
  3. customthen partitioned between EtOAc and water
  4. customColumn chromatography (9:1 DCM/MeOH) gave a solid which
  5. customwas then reprecipitated from DCM/MeOH

Sources & evidence

ORD record
ord-704c6fcb04a849629c1901cbeb6d0f67
Source dataset
uspto-grants-2010_02
Patent number
US07666864B2

Reaction notes

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