Diisopropylcarbodiimide → [(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 1-oxide

HRID 459040

Reaction equation

HRID 459040 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.[C:33](O)(=[O:41])[C:34]1[CH:39]=[CH:38][CH:37]=[N+:36]([O-:40])[CH:35]=1.C(N=C=NC(C)C)(C)C>CN(C)C1C=CN=CC=1.CN(C=O)C.CO.C(OCC)C>[C:33]([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:34]1[CH:39]=[CH:38][CH:37]=[N+:36]([O-:40])[CH:35]=1

Participants

8

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 16976Oxiniacic AcidHCID 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 58758458[(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 1-oxideYield 53.6%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

(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 (Example 1: 130 mg, 0.30 mMol), nicotinic acid 1-oxide (100 mg, 0.72 mMol), 1,3-diisopropylcarbodiimide (290 mg, 2.3 mMol), and 4-dimethylaminopyridine (5 mg, 0.04 mMol) were suspended in 2 ml of DMF at room temperature. The mixture was stirred one day, diluted with methanol (2 ml), stirred 5 minutes and then further diluted with diethyl ether (20 ml) to give a suspension. The solids were collected and rinsed with diethyl ether, then suspended in acetonitrile:methanol (1:1, 150 ml), the mixture was warmed and stirred a few minutes, then allowed to cool. The suspension was filtered and the filtrate was concentrated to a volume of 10 ml to give a suspension. The solids were collected, rinsed with acetonitrile, then diethyl ether and dried under vacuum to yield the title compound as an off-white solid (90 mg), melting point: 255° C.

Workup

  1. stirringstirred 5 minutes
  2. customto give a suspension
  3. customThe solids were collected
  4. washrinsed with diethyl ether
  5. temperaturethe mixture was warmed
  6. stirringstirred a few minutes
  7. temperatureto cool
  8. filtrationThe suspension was filtered
  9. concentrationthe filtrate was concentrated to a volume of 10 ml
  10. customto give a suspension
  11. customThe solids were collected
  12. washrinsed with acetonitrile
  13. dry with materialdiethyl ether and dried under vacuum

Sources & evidence

ORD record
ord-598a5b9bc0424f4e9dcb84c1dc15e0fa
Source dataset
uspto-grants-2007_03
Patent number
US07192974B2

Linked notes

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