Formaldehyde → 2-(2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine

HRID 2387611Notes

Reaction equation

HRID 2387611 reaction equation
[N:1]([CH2:4][CH2:5][CH2:6][C:7]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:11]([C:12]2[S:13][C:14]3[CH2:15][NH:16][CH2:17][CH2:18][C:19]=3[N:20]=2)[N:10]=[C:9]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[F:28])[S:8]1)=[N+:2]=[N-:3].C=O.[C:37](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])([O-])=O.[Na+].[Na+]>ClCCCl>[N:1]([CH2:4][CH2:5][CH2:6][C:7]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:11]([C:12]2[S:13][C:14]3[CH2:15][N:16]([CH3:37])[CH2:17][CH2:18][C:19]=3[N:20]=2)[N:10]=[C:9]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[F:28])[S:8]1)=[N+:2]=[N-:3]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 866087722-(2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine

Product 1

HCID 866087732-(2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridineYield 89.9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 2-(2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (0.050 g, 0.100 mmol) in 1 mL DCE was added formaldehyde (0.033 g, 37 wt % in water, 0.401 mmol) followed by sodium triacetoxyborohydride (0.023 g, 0.110 mmol). The resulting suspension was stirred vigorously at room temperature overnight then was treated with saturated Na2CO3 solution (10 mL) and stirred for 10 minutes. The mixture was extracted with EtOAc (3×10 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 (0-3% MeOH/DCM) to afford the desired product as a yellow foam (0.046 g, 89%).

Workup

  1. stirringstirred for 10 minutes
  2. extractionThe mixture was extracted with EtOAc (3×10 mL)
  3. washthe combined organic phases were washed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography (0-3% MeOH/DCM)

Sources & evidence

ORD record
ord-98c04a9b304e4b09a7a4e91881482825
Source dataset
uspto-grants-2012_09
Patent number
US08268871B2

Reaction notes

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