Diisopropylethylamine → 3-(5-(2,5-Difluorophenyl)-3-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)-2-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)propan-1-amine

HRID 2387609Notes

Reaction equation

HRID 2387609 reaction equation
S1C2CCC(C([O-])=O)NC=2N=C1.[N:13]([CH2:16][CH2:17][CH2:18][C:19]1([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[N:23]([C:24](=[S:26])[NH2:25])[N:22]=[C:21]([C:27]2[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=2[F:34])[S:20]1)=[N+]=[N-].Br[CH:42]1[C:47](=O)[CH2:46][CH2:45][N:44]([C:49](OC(C)(C)C)=O)[CH2:43]1.CCN(C(C)C)C(C)C>C(O)C>[F:34][C:28]1[CH:29]=[CH:30][C:31]([F:33])=[CH:32][C:27]=1[C:21]1[S:20][C:19]([CH2:18][CH2:17][CH2:16][NH2:13])([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[N:23]([C:24]2[S:26][C:42]3[CH2:43][N:44]([CH3:49])[CH2:45][CH2:46][C:47]=3[N:25]=2)[N:22]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 106839701-tert-Butyloxycarbonyl-3-bromo-4-oxopiperidine2×HCID 866087702-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazole-3(2H)-carbothioamideHCID 866493676,7-dihydrothiazolo[5,4-e]pyridine-5(4H)-carboxylate

Product 1

HCID 119599503-(5-(2,5-Difluorophenyl)-3-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)-2-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)propan-1-amineYield 89.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Preparation of tert-butyl 24243-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-6,7-dihydrothiazolo[5,4-e]pyridine-5(4H)-carboxylate: To a solution of 2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazole-3(2H)-carbothioamide (0.300 g, 0.717 mmol) in 10 mL of ethanol was added tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate (0.239 g, 0.860 mmol) followed by DIEA (0.25 mL, 1.43 mmol). The mixture was allowed to stir overnight at reflux then treated with tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate (100 mg) and stirred at reflux for a further 3 hrs. The cooled mixture was partitioned between saturated NaHCO3 solution (30 mL) and EtOAc (30 mL) and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic phases were washed with brine (20 mL) dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (5-10% ethyl acetate/hexanes) to afford the desired product as a bright yellow foam (0.313 g, 73%).

Workup

  1. temperatureat reflux
  2. stirringstirred
  3. temperatureat reflux for a further 3 hrs
  4. customThe cooled mixture was partitioned between saturated NaHCO3 solution (30 mL) and EtOAc (30 mL)
  5. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  6. washThe combined organic phases were washed with brine (20 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography (5-10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8b5660e45f9d4c2584499b8cbd805f34
Source dataset
uspto-grants-2012_09
Patent number
US08268871B2

Reaction notes

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