Pyridine → HCID 58758457, compound

HRID 459036Notes

Reaction equation

HRID 459036 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.N1C=CC=C[CH:34]=1.[C:39]1(=[O:49])[O:44][C:42](=[O:43])[C@H:41]2[CH2:45][CH2:46][CH2:47][CH2:48][C@@H:40]12>CN(C)C=O.CN(C)C1C=CN=CC=1>[CH:40]1([C:39]([O:20][CH2:19][C@H:17]2[O:16][N:15]=[C:14]([C:11]3[CH:12]=[CH:13][C:8]([C:7]4[CH:6]=[CH:5][C:4]([N:21]5[CH2:25][C@H:24]([CH2:26][N:27]6[CH:31]=[CH:30][N:29]=[N:28]6)[O:23][C:22]5=[O:32])=[CH:3][C:2]=4[F:1])=[CH:9][N:10]=3)[CH2:18]2)=[O:49])[CH2:48][CH2:47][CH2:46][CH2:45][CH:41]1[C:42]([O:44][CH3:34])=[O:43]

Participants

6

Reactant 3

HCID 1049PyridineHCID 641660Hexahydrophthalic anhydride, cis-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 58758457HCID 58758457, compoundYield 50.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

(5R)-3-(3-Fluoro-4-{6-[(5S)-5-(hydroxymethyl)-4,5-dihydro-3-isoxazolyl]-3-pyridinyl}phenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (Example 1, 60 mg, 0.13 mmol) was suspended in 2 mL of anhydrous dimethylformamide. Anhydrous pyridine (1 mL, 12 mmol), 4-dimethylaminopyridine (MAP) (10 mg, 0.08 mmol) and cis-hexahydrophthalic anhydride (85 mg, 0.55 mmol) were added and the solution was stirred for 16 hours at room temperature during which the mixture became a clear solution. The reaction was quenched with 1 mL of methanol and purged with diazomethane generated from 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) in a diazomethanegenerator (Aldrich, cat. No. Z41,173-6) until all product was converted into its methyl ester as judged by LCMS and the solution turned yellow by excess diazomethane. The solvent was removed and the product purified by chromatography on silica using a gradient from 0–20% methanol in dichloromethane that yielded 40 mg (48%) of the title compound as an off white solid.

Workup

  1. customThe reaction was quenched with 1 mL of methanol
  2. custompurged with diazomethane
  3. customThe solvent was removed
  4. customthe product purified by chromatography on silica using a gradient from 0–20% methanol in dichloromethane that

Sources & evidence

ORD record
ord-1a30375b6d8c452da3c42dda71c44843
Source dataset
uspto-grants-2007_03
Patent number
US07192974B2

Reaction notes

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