Trifluoroacetic acid → 3-n-Butyl-1-[2-chloro-5-(propionylamino)phenyl]-4-[(3-fluoro-2'-sulfamoylbiphenyl-4-yl)methyl]-1H-pyrazole-5-carbonitrile

HRID 257570Notes

Reaction equation

HRID 257570 reaction equation
[CH2:1]([C:5]1[C:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[S:23](=[O:30])(=[O:29])[NH:24]C(C)(C)C)=[CH:13][C:12]=2[F:31])=[C:8]([C:32]#[N:33])[N:7]([C:34]2[CH:39]=[C:38]([NH:40][C:41](=[O:44])[CH2:42][CH3:43])[CH:37]=[CH:36][C:35]=2[Cl:45])[N:6]=1)[CH2:2][CH2:3][CH3:4].C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>>[CH2:1]([C:5]1[C:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[S:23](=[O:30])(=[O:29])[NH2:24])=[CH:13][C:12]=2[F:31])=[C:8]([C:32]#[N:33])[N:7]([C:34]2[CH:39]=[C:38]([NH:40][C:41](=[O:44])[CH2:42][CH3:43])[CH:37]=[CH:36][C:35]=2[Cl:45])[N:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 197831473-n-Butyl-4-[[2'-(N-t-butylsulfamoyl)-3-fluorobiphenyl-4-yl]methyl]-1-[2-chloro-5-(propionylamino)phenyl]-1H-pyrazole-5-carbonitrile

Product 1

HCID 197832113-n-Butyl-1-[2-chloro-5-(propionylamino)phenyl]-4-[(3-fluoro-2'-sulfamoylbiphenyl-4-yl)methyl]-1H-pyrazole-5-carbonitrileYield 97.3%

Procedure

A mixture of 142 mg (0.218 mmol) of 3-n-butyl-4-[[2'-(N-t-butylsulfamoyl)-3-fluorobiphenyl-4-yl]methyl]-1-[2-chloro-5-(propionylamino)phenyl]-1H-pyrazole-5-carbonitrile (from Step J), 237 μL (236 mg, 2.18 mmol) of anisole, and 675 μL of trifluoroacetic acid (TFA) was stirred at room temperature overnight in a stoppered flask. The mixture was evaporated under a stream of N2, and the residue was flash chromatographed on silica gel (elution with 1% and then 3% MeOH in CH2Cl2), yielding 126 mg (97%) of the title compound as a slightly yellow, stiff foam; nearly homogeneous by TLC in 95:5 CH2Cl2 --MeOH; mass spectrum (FAB) m/e 594 (M+1)+. 400 MHz 1H NMR (CDCl3) δ0.93 (t, J=7.3 Hz, 3H), 1.20 (t, J=7.5 Hz, 3H), 1.40 (m, 2H), 1.67 (m, 2H), 2.37 (q, J=7.5 Hz, 2H), 2.69 (t, J=7.8 Hz, 2H), 4.02 (s, 2H), 4.52 (s, 2H), 7.2-7.6 (m, 8H), 7.81 (d, J=2.5 Hz, 1H), 8.15 (dd, J=8.0, 1.3 Hz, 1H).

Workup

  1. customThe mixture was evaporated under a stream of N2
  2. customchromatographed on silica gel (
  3. washelution with 1%

Sources & evidence

ORD record
ord-be646c082131412093d94476fdbdc201
Source dataset
uspto-grants-1993_11
Patent number
US05262412

Reaction notes

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