Formaldehyde → 1-[2-(3-Dimethylaminopropyl)-5-(3-fluorophenyl)-2-phenyl-[1,3,4]thiadiazol-3-yl]-2-methylpropan-1-one

HRID 883099Notes

Reaction equation

HRID 883099 reaction equation
N[CH2:2][CH2:3][CH2:4][C:5]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:9]([C:10](=[O:14])[CH:11]([CH3:13])[CH3:12])[N:8]=[C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[S:6]1.[CH2:28]=O.[C:30]([BH3-])#[N:31].[Na+]>CO.[Na+].[Cl-]>[CH3:28][N:31]([CH3:30])[CH2:2][CH2:3][CH2:4][C:5]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:9]([C:10](=[O:14])[CH:11]([CH3:13])[CH3:12])[N:8]=[C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[S:6]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 250991931-(2-(3-aminopropyl)-5-(3-fluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-2-methylpropan-1-one

Product 1

HCID 601397971-[2-(3-Dimethylaminopropyl)-5-(3-fluorophenyl)-2-phenyl-[1,3,4]thiadiazol-3-yl]-2-methylpropan-1-oneYield 36.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 5234Sodium ChlorideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 1-(2-(3-aminopropyl)-5-(3-fluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-2-methylpropan-1-one (9.0 mg, 0.02 mmol) in MeOH (1 mL) was added paraformaldehyde (10 mg, 0.40 mmol). The mixture was heated to 70° C. for 2 hours. The mixture was allowed to cool to room temperature and sodium cyanoborohydride (0.07 mL, 0.07 mmol, 1M solution in THF) was added. After stirring for 40 minutes, the mixture was diluted with half saturated NaCl (50 mL) and extracted with ethyl acetate (3×25 mL). The combined organics were washed with saturated NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (2% triethylamine, 40% ethyl acetate in hexanes) to provide the final product (3.0 mg, 30%) as pale yellow film. MS ESI (+) m/z 414 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 7.44 (m, 3H), 7.36 (m, 5H), 7.14 (m, 1H), 3.51 (m, 1H), 3.17 (m, 1H), 2.40 (m, 3H), 2.23 (s, 6H), 1.92 (m, 1H), 1.53 (m, 1H), 1.20 (d, 3H, J=7 Hz), 1.18 (d, 3H, J=7 Hz).

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with ethyl acetate (3×25 mL)
  3. washThe combined organics were washed with saturated NaCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography (2% triethylamine, 40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-19726b07c1104100bf5c07343ea7f565
Source dataset
uspto-grants-2012_08
Patent number
US08236825B2

Reaction notes

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