1H-1,2,4-Triazole → 6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-3-(1H-1,2,4-triazol-1-yl)benzo[d]isoxazole-5-carbaldehyde

HRID 245543Notes

Reaction equation

HRID 245543 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[N:6][CH:5]=[N:4]1.Cl[C:9]1[C:13]2[CH:14]=[C:15]([CH:27]=[O:28])[C:16]([N:19]3[CH2:24][C@@H:23]([CH3:25])[O:22][C@H:21]([CH3:26])[CH2:20]3)=[C:17]([F:18])[C:12]=2[O:11][N:10]=1>CN(C=O)C.C(Cl)Cl>[CH3:26][C@@H:21]1[CH2:20][N:19]([C:16]2[C:15]([CH:27]=[O:28])=[CH:14][C:13]3[C:9]([N:3]4[CH:7]=[N:6][CH:5]=[N:4]4)=[N:10][O:11][C:12]=3[C:17]=2[F:18])[CH2:24][C@@H:23]([CH3:25])[O:22]1

Participants

6

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 866581223-chloro-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-5-carbaldehyde2×

Product 1

HCID 866581356-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-3-(1H-1,2,4-triazol-1-yl)benzo[d]isoxazole-5-carbaldehyde

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Sodium hydride (60% dispersion) (0.288 g, 7.19 mmol) was added to a solution of 1H-1,2,4-triazole (0.530 g, 7.67 mmol) and 3-chloro-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-5-carbaldehyde (Intermediate 535, 1.5 g, 4.80 mmol) in DMF (10 ml), and the mixture was stirred at room temperature overnight. The mixture was quenched with aqueous NH4Cl and diluted with water before being extracted with CH2Cl2 5 times. The combined extracts were dried (MgSO4) and concentrated to give a solid that was taken up in CH2Cl2. Insoluble solids were filtered off and rinsed with additional CH2Cl2. The solids were dried in vacuo and were consistent with desired product. The filtrate was concentrated and chromatographed on silica gel (100% CH2Cl2 followed by gradient elution to 50% EtOAc in CH2Cl2) to give additional desired product. Total of 866 mg.

Workup

  1. customThe mixture was quenched with aqueous NH4Cl
  2. additiondiluted with water
  3. extractionbefore being extracted with CH2Cl2 5 times
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. concentrationconcentrated
  6. customto give a solid
  7. filtrationInsoluble solids were filtered off
  8. washrinsed with additional CH2Cl2
  9. customThe solids were dried in vacuo
  10. concentrationThe filtrate was concentrated
  11. customchromatographed on silica gel (100% CH2Cl2 followed by gradient elution to 50% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-57f57cbfbe1e4320ad9cb5c00301d120
Source dataset
uspto-grants-2014_02
Patent number
US08658641B2

Reaction notes

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