Sodium triacetoxyborohydride → 1-(4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)-N-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)methanamine

HRID 1397208Notes

Reaction equation

HRID 1397208 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[F:15][C:16]([F:31])([F:30])[C:17]1[O:21][N:20]=[C:19]([C:22]2[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=2)[CH:25]=O)[N:18]=1.[C:32]1([C:38]2[N:39]=[C:40]([C:43]3([CH2:49][NH2:50])[CH2:48][CH2:47][O:46][CH2:45][CH2:44]3)[S:41][CH:42]=2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>ClC(Cl)C>[C:32]1([C:38]2[N:39]=[C:40]([C:43]3([CH2:49][NH:50][CH2:25][C:24]4[CH:27]=[CH:28][CH:29]=[C:22]([C:19]5[N:18]=[C:17]([C:16]([F:31])([F:30])[F:15])[O:21][N:20]=5)[CH:23]=4)[CH2:44][CH2:45][O:46][CH2:47][CH2:48]3)[S:41][CH:42]=2)[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 185454733-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzaldehydeHCID 67322930(4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methanamine

Product 1

HCID 699499611-(4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)-N-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)methanamineYield 22%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Sodium triacetoxy borohydride (200 mg, 0.9 mmol) was added to a solution of 3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzaldehyde (140 mg, 0.6 mmol) and (4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methanamine (170 mg, 0.6 mmol) in dry dichloroethane (20 mL) at 0° C. under nitrogen atmosphere and stirred at room temperature for 8 h. The reaction mixture was carefully quenched with 10% NaHCO3 solution and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluent 20-25% EtOAc in petroleum ether) to get 1-(4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)-N-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)methanamine (65 mg, yield 22%): 1H NMR (400 MHz, CDCl3) δ 7.98 (m, 2H), 7.89 (d, J=7.6 Hz, 2H), 7.48 (s, 1H), 7.46-7.27 (m, 5H), 3.86-3.81 (m, 4H), 3.69-3.64 (m, 2H), 2.91 (s, 2H), 2.36 (m, 2H), 2.03-1.97 (ddd, J=13.7 Hz, 9.7 Hz, 4 Hz, 2H). MS (ESI) m/z: Calculated for C25H23F3N4O2S: 500.15. found: 501.0 (M−H)−.

Workup

  1. customThe reaction mixture was carefully quenched with 10% NaHCO3 solution
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluent 20-25% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-a867969a2e7c4e708ae72814a29386a4
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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