Dimethylformamide → HCID 86595574, compound

HRID 402237Notes

Reaction equation

HRID 402237 reaction equation
[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:25]([CH:26]=[O:27])[CH2:24][CH2:23][CH2:22][C:21]([C:28](O)=[O:29])=[CH:20][C:19]=3[CH:31]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].CN(C=O)C.C(Cl)(=O)C(Cl)=O.[CH2:43]([N:46]1[C:50]([CH2:51][S:52]([C:54]2[CH:60]=[CH:59][C:57]([NH2:58])=[CH:56][CH:55]=2)=[O:53])=[CH:49][N:48]=[CH:47]1)[CH2:44][CH3:45]>O1CCCC1.O.N1C=CC=CC=1>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:25]([CH:26]=[O:27])[CH2:24][CH2:23][CH2:22][C:21]([C:28]([NH:58][C:57]4[CH:56]=[CH:55][C:54]([S:52]([CH2:51][C:50]5[N:46]([CH2:43][CH2:44][CH3:45])[CH:47]=[N:48][CH:49]=5)=[O:53])=[CH:60][CH:59]=4)=[O:29])=[CH:20][C:19]=3[CH:31]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 229386104-[[(1-Propyl-1H-imidazol-5-yl)methyl]sulfinyl]benzenamineHCID 86595575HCID 86595575, compound

Product 1

HCID 86595574HCID 86595574, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

(−)-4-(((1-Propylimidazol-5-yl)methyl)sulfinyl)aniline di-p-toluoyl-D-tartarate monohydrate (6.58 g) was dissolved in ethyl acetate (50 ml) and 1N hydrochloric acid (33.5 ml), followed by separation. To the aqueous layer was added an aqueous 25% potassium carbonate solution (33.5 ml), followed by extraction with 2-propanol-ethyl acetate (1:4) twice. The organic layers were combined and washed with saturated brine, dried with magnesium sulfate, and the solvent was distilled off under reduced pressure. To the resulting residue tetrahydrofuran was added, after which the solvent was distilled off again under reduced pressure to give (−)-4-(((1-propylimidazol-5-yl)methyl)sulfinyl)aniline. Then, to a solution of 8-(4-(2-butoxyethoxy)phenyl)-1-formyl-1,2,3,4-tetrahydro-1-benzoazocine-5-carboxylic acid (3.0 g) in tetrahydrofuran (30 ml) was added a drop of DMF, and then oxalyl chloride (0.86 ml) was added, and the mixture was stirred under nitrogen atmosphere for 1 hour. The resulting solution was added dropwise to a solution of (−)-4-(((1-propylimidazol-5-yl)methyl)sulfinyl)aniline and pyridine (16 ml) in tetrahydrofuran (70 ml) at 0° C. under nitrogen atmosphere. The mixture was returned to room temperature and stirred for 3 hours, after which water was added and extracted with ethyl acetate. The organic layer was washed with 10% aqueous acetic acid solution twice, with aqueous saturated sodium bicarbonate solution twice, and with saturated brine once, after which the resultant was dried with magnesium sulfate. After distilling off the solvent under reduced pressure, the resultant was separated and purified with a basic silica gel column chromatography (methanol:ethyl acetate=1:25) to give (−)-8-[4-(2-butoxyethoxy)phenyl]-1-formyl-N-[4-[[[1-propylimidazol-5-yl]methyl]sulfinyl]phenyl]-1,2,3,4-tetrahydro-1-benzoazocine-5-carboxamide (3.34 g) (Compound 29) as a yellow amorphous material.

Workup

  1. customwas returned to room temperature
  2. stirringstirred for 3 hours
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with 10% aqueous acetic acid solution twice
  5. dry with materialwith aqueous saturated sodium bicarbonate solution twice, and with saturated brine once, after which the resultant was dried with magnesium sulfate
  6. distillationAfter distilling off the solvent under reduced pressure
  7. customthe resultant was separated
  8. custompurified with a basic silica gel column chromatography (methanol:ethyl acetate=1:25)

Sources & evidence

ORD record
ord-4f7eda47824e4b5ab141ddcc761edae8
Source dataset
uspto-grants-2014_06
Patent number
US08741943B2

Reaction notes

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