Diisopropylethylamine → 4-((3-ethylphenyl)(2-methyl-5-phenyl-2H-1,2,4-triazol-3-yl)methylamino)-3-fluorobenzonitrile
Reaction equation
CS(OS(C)(=O)=O)(=O)=O.C(C1C=C([CH:18]([C:20]2[N:21]([CH3:31])[N:22]=[C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:24]=2)O)C=CC=1)C.C(N([CH:38]([CH3:40])[CH3:39])CC)(C)C.[NH2:41][C:42]1[CH:49]=[CH:48][C:45]([C:46]#[N:47])=[CH:44][C:43]=1[F:50]>C(Cl)Cl>[CH2:27]([C:26]1[CH:25]=[C:23]([N:41]([CH2:18][C:20]2[N:21]([CH3:31])[N:22]=[C:23]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:24]=2)[C:42]2[CH:49]=[CH:48][C:45]([C:46]#[N:47])=[CH:44][C:43]=2[F:50])[CH:40]=[CH:38][CH:39]=1)[CH3:28]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
Methansulfonic anhydride (77 mg, 0.44 mmol) was added to a solution of Intermediate 370.2 (81 mg, 0.28 mmol) and diisopropylethylamine (0.2 mL, 1.16 mmol) in CH2Cl2 (2.5 mL) at 0° C. The mixture was stirred for 1 h at 0° C. and then 4-amino-3-fluorobenzonitrile (136 mg, 1 mmol) was added. The mixture was stirred for 1 h at ambient temperature, diluted with CH2Cl2 (40 mL), washed with sat. NaHCO3 and brine, dried (Na2SO4) and concentrated. Purification by flash chromatography (EtOAc, hexanes) afforded 65 mg of Intermediate 382.1. 1H NMR (400 MHz, CDCl3) δ ppm 1.11 (t, J=7.58 Hz, 3H) 2.54 (q, J=7.58 Hz, 2H) 3.69 (s, 3 H) 5.60 (d, J=5.87 Hz, 1H) 6.10-6.16 (m, J=1.96 Hz, 1H) 7.06-7.24 (m, 6H) 7.27-7.39 (m, 3H) 7.99-8.04 (m, 2H).
Workup
- stirringThe mixture was stirred for 1 h at ambient temperature
- washwashed with sat. NaHCO3 and brine
- dry with materialdried (Na2SO4)
- concentrationconcentrated
- customPurification by flash chromatography (EtOAc, hexanes)
Sources & evidence
- ORD record
- ord-204e4d0995da41528539c0eb265fc126
- Source dataset
- uspto-grants-2009_08
- Patent number
- US07576098B2
Reaction notes
Loading…