Acetone → 1-[5-(3-Fluorophenyl)-2-(3-isopropylaminopropyl)-2-phenyl-[1,3,4]thiadiazol-3-yl]-2-methylpropan-1-one

HRID 270499Notes

Reaction equation

HRID 270499 reaction equation
[NH2:1][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.[CH3:28][C:29]([CH3:31])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(#N)C.C([O-])([O-])=O.[Na+].[Na+]>[F:21][C:17]1[CH:16]=[C:15]([C:7]2[S:6][C:5]([CH2:4][CH2:3][CH2:2][NH:1][CH:29]([CH3:31])[CH3:28])([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:9]([C:10](=[O:14])[CH:11]([CH3:13])[CH3:12])[N:8]=2)[CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 180Acetone2×HCID 5049666Sodium triacetoxyborohydride2×HCID 250991931-(2-(3-aminopropyl)-5-(3-fluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-2-methylpropan-1-one

Product 1

HCID 601398401-[5-(3-Fluorophenyl)-2-(3-isopropylaminopropyl)-2-phenyl-[1,3,4]thiadiazol-3-yl]-2-methylpropan-1-oneYield 63.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 10340Sodium CarbonateSolvent

Procedure

A mixture 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) and acetone (20 mg, 0.40 mmol) in acetonitrile (0.5 mL) was stirred at room temperature for 1 hour. To the mixture was added sodium triacetoxyborohydride (33 mg, 0.20 mmol). After stirring at room temperature for 16 hours, more acetone (50 μL) and sodium triacetoxyborohydride (14 mg) was added. The reaction mixture was heated to 45° C. for 40 hours and then diluted with 10% Na2CO3 (30 mL). The mixture was extracted with ethyl acetate (3×30 mL). The combined organics were 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 product (5.4 mg, 50%) as pale yellow film. MS ESI (+) m/z 428 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 7.45 (d, 2H, J=8 Hz), 7.42 (d, 1H, J=7 Hz), 7.37 (m, 4H), 7.27 (m, 1H), 7.14 (m, 1H), 3.50 (m, 1H), 3.21 (m, 1H), 2.80 (m, 1H), 2.73 (m, 2H), 2.39 (m, 1H), 1.95 (m, 1H), 1.56 (m, 1H), 1.19 (d, 3H, J=6 Hz), 1.17 (d, 3H, J=6 Hz), 1.05 (d, 6H, J=6 Hz).

Workup

  1. stirringAfter stirring at room temperature for 16 hours
  2. temperatureThe reaction mixture was heated to 45° C. for 40 hours
  3. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
  4. dry with materialThe combined organics were dried 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-9d148d18ee8541f681ea99427a9476b4
Source dataset
uspto-grants-2008_11
Patent number
US07449486B2

Reaction notes

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