Dimethylamine → 2-(2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-N,N-dimethylthiazole-4-carboxamide

HRID 1508407Notes

Reaction equation

HRID 1508407 reaction equation
[CH3:1][NH:2][CH3:3].C[Al](C)C.[N:8]([CH2:11][CH2:12][CH2:13][C:14]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[N:18]([C:19]2[S:20][CH:21]=[C:22]([C:24]([O:26]CC)=O)[N:23]=2)[N:17]=[C:16]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[F:36])[S:15]1)=[N+:9]=[N-:10].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1COCC1>[N:8]([CH2:11][CH2:12][CH2:13][C:14]1([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[N:18]([C:19]2[S:20][CH:21]=[C:22]([C:24]([N:2]([CH3:3])[CH3:1])=[O:26])[N:23]=2)[N:17]=[C:16]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[F:36])[S:15]1)=[N+:9]=[N-:10]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 9357Potassium Sodium TartrateHCID 16682925TrimethylaluminumHCID 86608779ethyl 2-(2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)thiazole-4-carboxylate

Product 1

HCID 866493712-(2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-N,N-dimethylthiazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of dimethylamine (0.102 mL, 2.0 M, 0.2 mmol) in 1 mL of anhydrous THF was added trimethylaluminum (0.102 mL, 2.0 M, 0.2 mmol). The solution was stirred at room temperature for 15 minutes, then treated with a solution of ethyl 2-(2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)thiazole-4-carboxylate (0.035 g, 0.07 mmol) in 0.5 mL of anhydrous THF. After stirring at room temperature for 16 hours the mixture was treated with 0.5 N aqueous Rochelle's salt solution (10 mL), then partitioned between saturated NH4Cl (10 mL) and EtOAc (10 mL). The aqueous layer was extracted with EtOAc (2×10 mL) and the combined organic phases were washed with brine (10 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (20-35% ethyl acetate/hexanes) to afford the desired product as a yellow gum, 0.026 g, 74%.

Workup

  1. stirringAfter stirring at room temperature for 16 hours the mixture
  2. custompartitioned between saturated NH4Cl (10 mL) and EtOAc (10 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  4. washthe combined organic phases were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (20-35% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-3595fd08b8614b76b9b6872468a977e6
Source dataset
uspto-grants-2015_12
Patent number
US09221841B2

Reaction notes

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