1,3,4-Thiadiazol-2-amine → N-(3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropyl)-1,3,4-thiadiazol-2-amine

HRID 218157Notes

Reaction equation

HRID 218157 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:18]([CH3:22])([CH3:21])[CH:19]=O)=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[S:29]1[CH:33]=[N:32][N:31]=[C:30]1[NH2:34].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)CCl.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:18]([CH3:22])([CH3:21])[CH2:19][NH:34][C:30]4[S:29][CH:33]=[N:32][N:31]=4)=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 199091,3,4-Thiadiazol-2-amineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 592510413-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanal

Product 1

HCID 24937094N-(3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropyl)-1,3,4-thiadiazol-2-amineYield 19%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred solution of 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanal (419 mg, 1.12 mmol) in ClCH2CH2Cl (20 mL) was added 1,3,4-thiadiazol-2-amine (137 mg, 1.35 mmol) and titanium tetraisopropoxide (0.35 mL, 1.2 mmol) at RT under nitrogen. The reaction mixture was heated at 85° C. for 1 hr then sodium triacetoxyborohydride (318 mg, 1.5 mmol) was added and the reaction was heated at 85° C. for 4 hr. The reaction mixture was poured into a sat. sodium bicarbonate solution (100 mL), extracted with CH2Cl2 (100 mL), dried (Na2SO4) and concentrated. The final product was purified using HPLC to give 95 mg (19% yield) of N-(3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropyl)-1,3,4-thiadiazol-2-amine which showed consistent 1H-NMR spectra. MS found: (M+H)+=458. NMR (CDCl3) δ 11.3 (bs, 1H); 8.12 (s, 1H); 8.03 (s, 1H); 7.82 (s, 1H); 7.52-7.55 (m, 2H); 7.48 (s, 1H); 7.39-7.41 (d, 2H); 7.11-7.23 (m, 5H); 4.16 (s, 1H), 3.09-3.18 (q, 2H); 1.18 (s, 6H).

Workup

  1. temperaturethe reaction was heated at 85° C. for 4 hr
  2. extractionextracted with CH2Cl2 (100 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe final product was purified

Sources & evidence

ORD record
ord-3abfb9f9f639450eaad490a561ee1293
Source dataset
uspto-grants-2012_06
Patent number
US08198311B2

Reaction notes

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