4-Methylmorpholine → HCID 71509623, compound

HRID 1404209Notes

Reaction equation

HRID 1404209 reaction equation
[C:1]1([CH3:25])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]1[CH2:16][CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:17][C:18]3[S:19][C:20]([CH2:23][NH2:24])=[CH:21][N:22]=3)[CH:13]=2)[O:8]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[O:55]1[C:59]([C:60](O)=[O:61])=[CH:58][CH:57]=[N:56]1>CN(C=O)C.O>[C:1]1([CH3:25])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]1[CH2:16][CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:17][C:18]3[S:19][C:20]([CH2:23][NH:24][C:60]([C:59]4[O:55][N:56]=[CH:57][CH:58]=4)=[O:61])=[CH:21][N:22]=3)[CH:13]=2)[O:8]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 20605991,2-Oxazole-5-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 71292807HCID 71292807, compound

Product 1

HCID 71509623HCID 71509623, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of [2-(2-o-tolyl-chroman-6-yloxy)-thiazol-5-ylmethyl]amine (150 mg, 0.43 mmol) in DMF (2 ml), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (114 mg, 0.60 mmol, 1.4 eq), 1-hydroxy-benzotriazole (81 mg, 0.60 mmol, 1.4 eq) and N-methylmorpholine (107 mg, 1.07 mmol, 2.5 eq) and isoxazole-5-carboxylic acid (72 mg, 0.64 mmol, 1.5 eq) were added. The mixture was stirred for 16 h, then diluted with water, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with a diluted aqueous solution of sodium carbonate and brine, dried over sodium sulfate and filtered, and the solvent was removed under reduced pressure. The crude product was purified by column chromatography (silica gel, ethyl acetate/methanol gradient). Isoxazole-5-carboxylic acid [2-(2-o-tolyl-chroman-6-yloxy)-thiazol-5-ylmethyl]-amide (112 mg, 59%) was obtained as a white solid.

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate
  2. washThe combined organic layers were washed with a diluted aqueous solution of sodium carbonate and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customThe crude product was purified by column chromatography (silica gel, ethyl acetate/methanol gradient)

Sources & evidence

ORD record
ord-8305add2891147718ed93c657d3a94ba
Source dataset
uspto-grants-2014_12
Patent number
US08912224B2

Reaction notes

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