Dimethylformamide → [(5S)-3-(5-{2-Fluoro-4-[(5R)-2-oxo-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-3-yl]phenyl}pyridin-2-yl)-4,5-dihydroisoxazol-5-yl]methyl nicotinate

HRID 459023Notes

Reaction equation

HRID 459023 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:21]2[CH2:25][C@H:24]([CH2:26][N:27]3[CH:31]=[CH:30][N:29]=[N:28]3)[O:23][C:22]2=[O:32])[CH:5]=[CH:6][C:7]=1[C:8]1[CH:9]=[N:10][C:11]([C:14]2[CH2:18][C@@H:17]([CH2:19][OH:20])[O:16][N:15]=2)=[CH:12][CH:13]=1.Cl.[C:34](Cl)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[N:37][CH:36]=1.CN(C)C=O>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[C:34]([O:20][CH2:19][C@H:17]1[O:16][N:15]=[C:14]([C:11]2[CH:12]=[CH:13][C:8]([C:7]3[CH:6]=[CH:5][C:4]([N:21]4[CH2:25][C@H:24]([CH2:26][N:27]5[CH:31]=[CH:30][N:29]=[N:28]5)[O:23][C:22]4=[O:32])=[CH:3][C:2]=3[F:1])=[CH:9][N:10]=2)[CH2:18]1)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[N:37][CH:36]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 9932836(5R)-3-(3-Fluoro-4-{6-[(5S)-5-(hydroxymethyl)-4,5-dihydroisoxazol-3-yl]pyridin-3-yl}phenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one

Product 1

HCID 58758440[(5S)-3-(5-{2-Fluoro-4-[(5R)-2-oxo-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-3-yl]phenyl}pyridin-2-yl)-4,5-dihydroisoxazol-5-yl]methyl nicotinateYield 48.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

(5R)-3-(3-Fluoro {6-[(5S)-5-(hydroxymethyl)-4,5,-dihydroisoxazol-3-yl]pyridin-3-yl}phenyl)-4-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (Example 1, 200 mg, 0.46 mM), nicotinoylchloride hydrochloride (175 mg, 0.98 mM), 4-(dimethylamino)pyridine (DMAP, 20 mg, 0.17 mM) were placed in a flask. Anhydrous dimethylformamide (2 mL) and anhydrous pyridine (2 mL) were added and the suspension was stirred for 16 hours during which it became a clear solution. 500 mg silicagel was added and the solvents were evaporated. The residue was chromatographed on silicagel eluting with a gradient of methanol in dichloromethane (1–20%) to give title compound (120 mg, 48%).

Workup

  1. addition500 mg silicagel was added
  2. customthe solvents were evaporated
  3. customThe residue was chromatographed
  4. washon silicagel eluting with a gradient of methanol in dichloromethane (1–20%)

Sources & evidence

ORD record
ord-781b09f1f4754cdf896f273bd21c90de
Source dataset
uspto-grants-2007_03
Patent number
US07192974B2

Reaction notes

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