Water → N-(4-Methoxybenzyl)-1,2,4-thiadiazol-5-amine

HRID 1473316Notes

Reaction equation

HRID 1473316 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.[S:11]1[C:15]([NH2:16])=[N:14][CH:13]=[N:12]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>ClCCl.CC(C)[O-].CC(C)[O-].CC(C)[O-].Cl[Ti+3]>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH:16][C:15]2[S:11][N:12]=[CH:13][N:14]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 962WaterHCID 312444-MethoxybenzaldehydeHCID 2902745-Amino-1,2,4-thiadiazoleHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 65271538N-(4-Methoxybenzyl)-1,2,4-thiadiazol-5-amine

Reagents, catalysts & solvents 2

HCID 11673339ChlorotitaniumtriisopropoxideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-methoxybenzaldehyde (10.0 g, 73.4 mmol) and 1,2,4-thiadiazol-5-amine (7.40 g, 73.4 mmol) in dichloromethane (200 mL) was added chlorotitanium triisopropoxide (28.6 g, 110 mmol) portionwise over 5 min. After stirring for 3 hours, sodium triacetoxyborohydride (38.9 g, 184 mmol) was added portionwise at 0° C. and allowed to stir for additional 1 hour. The reaction was cooled in an ice and water mixture, quenched with saturated NaHCO3 solution (300 mL) and extracted with dichloromethane (2×300 mL). The organic layer was separated, dried over Na2SO4, filtered and concentrated to obtain the product, which was purified by column chromatography using silica gel (100 to 200 mesh) and 0 to 30% ethyl acetate in hexane to give 5.5 g of as an off-white solid. MS (ESI, positive) m/z: 222.1; 1H NMR (400 MHz, DMSO-d6) δ 8.89 (s, 1H), 7.92 (s, 1H), 7.27 (d, J=8.5 Hz, 2H), 6.91 (d, J=8.5 Hz, 2H), 4.42 (d, J=5.4 Hz, 2H), 3.73 (s, 3H).

Workup

  1. stirringto stir for additional 1 hour
  2. customquenched with saturated NaHCO3 solution (300 mL)
  3. extractionextracted with dichloromethane (2×300 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto obtain the product, which
  9. customwas purified by column chromatography
  10. customto give 5.5 g of as an off-white solid

Sources & evidence

ORD record
ord-53d139c071e64f4d851f3c4b67874159
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…