Potassium Carbonate → N-(((5S)-3-(3-Fluoro-4-(2-((2-methyl-6-nitro-2,3-dihydroimi-dazo[2,1-b]oxazol-2-yl)methoxy)pyrimidin-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)-acetamide

HRID 1446074Notes

Reaction equation

HRID 1446074 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:17]2[CH2:21][C@H:20]([CH2:22][NH:23][C:24](=[O:26])[CH3:25])[O:19][C:18]2=[O:27])[CH:5]=[CH:6][C:7]=1B1OC(C)(C)C(C)(C)O1.Br[C:29]1[CH:30]=[N:31][C:32]([O:35][CH2:36][C:37]2([CH3:48])[O:41][C:40]3=[N:42][C:43]([N+:45]([O-:47])=[O:46])=[CH:44][N:39]3[CH2:38]2)=[N:33][CH:34]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.CCO.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:1][C:2]1[CH:3]=[C:4]([N:17]2[CH2:21][C@H:20]([CH2:22][NH:23][C:24](=[O:26])[CH3:25])[O:19][C:18]2=[O:27])[CH:5]=[CH:6][C:7]=1[C:29]1[CH:30]=[N:31][C:32]([O:35][CH2:36][C:37]2([CH3:48])[O:41][C:40]3=[N:42][C:43]([N+:45]([O-:47])=[O:46])=[CH:44][N:39]3[CH2:38]2)=[N:33][CH:34]=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 669556012-((5-Bromopyrimidin-2-yloxy)methyl)-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole

Product 1

HCID 44242748N-(((5S)-3-(3-Fluoro-4-(2-((2-methyl-6-nitro-2,3-dihydroimi-dazo[2,1-b]oxazol-2-yl)methoxy)pyrimidin-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)-acetamideYield 39.2%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
100 °C

Procedure

A mixture of (S)—N-((3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide (0.14 g, 0.37 mmol) and 2-((5-bromopyrimidin-2-yloxy)methyl)-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole (0.105 g, 0.29 mmol) in toluene (2.5 mL), EtOH (1.5 mL), DMF (4 mL) and K2CO3 (2 M, 1 mL, 2 mmol) was purged with nitrogen. PdCl2(dppf) (12 mg, 0.015 mmol) was added and the mixture was refluxed (100° C.) under nitrogen for 1 h, then partitioned between EtOAc (150 mL) and water (100 mL). The aqueous layer was re-extracted with 100 mL EtOAc. The organic layer was washed with brine, dried (Na2SO4) and evaporated, column chromatography using gradient elution (DCM/MeOH 0 to 5%) gave the title compound as a brown solid (60 mg, 39%). APCI MS m/z 528.3 (M+H). 1H NMR (400 MHz, (CD3)2SO) δ 8.81 (d, J=1.3 Hz, 2H), 8.22 (t, J=5.8 Hz, 1H), 8.16 (s, 1H), 7.68 (t, J=8.8 Hz, 1H), 7.65 (dd, J=13.4, 2.2 Hz, 1H), 7.45 (dd, J=8.6, 2.2 Hz, 1H), 4.81-4.73 (m, 1H), 4.71 (d, J=11.9 Hz, 1H), 4.67 (d, J=11.9 Hz, 1H), 4.45 (d, J=11.0 Hz, 1H), 4.23 (d, J=11.0 Hz, 1H), 4.18 (t, J=9.1 Hz, 1H), 3.79 (dd, J=9.2, 6.4 Hz, 1H), 3.44 (t, J=5.5 Hz, 2H), 1.84 (s, 3H), 1.73 (s, 3H).

Workup

  1. customwas purged with nitrogen
  2. custompartitioned between EtOAc (150 mL) and water (100 mL)
  3. extractionThe aqueous layer was re-extracted with 100 mL EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. washelution (DCM/MeOH 0 to 5%)

Sources & evidence

ORD record
ord-2453b09b334e4992986570e7881a587c
Source dataset
uspto-grants-2010_02
Patent number
US07666864B2

Reaction notes

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