Diisopropylethylamine → 4-((3,5-Dichloro-N-(4-fluorobenzyl)-2-hydroxyphenylsulfonamido)methyl)-N-(3,5-dichlorobenzyl)-N-(4-fluorobenzyl)benzamide

HRID 1889670Notes

Reaction equation

HRID 1889670 reaction equation
[Cl:1][C:2]1[C:3]([OH:31])=[C:4]([S:9]([N:12]([CH2:21][C:22]2[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][CH:23]=2)[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)(=[O:11])=[O:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[Cl:32][C:33]1[CH:34]=[C:35]([CH:46]=[C:47]([Cl:49])[CH:48]=1)[CH2:36][NH:37][CH2:38][C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[C:3]([OH:31])=[C:4]([S:9]([N:12]([CH2:21][C:22]2[CH:30]=[CH:29][C:25]([C:26]([N:37]([CH2:36][C:35]3[CH:46]=[C:47]([Cl:49])[CH:48]=[C:33]([Cl:32])[CH:34]=3)[CH2:38][C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)=[O:28])=[CH:24][CH:23]=2)[CH2:13][C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)(=[O:11])=[O:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58531400HCID 58531400, compoundHCID 58531427N-(3,5-Dichlorobenzyl)-1-(4-fluorophenyl)methanamine

Product 1

HCID 585314114-((3,5-Dichloro-N-(4-fluorobenzyl)-2-hydroxyphenylsulfonamido)methyl)-N-(3,5-dichlorobenzyl)-N-(4-fluorobenzyl)benzamideYield 53.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-((3,5-dichloro-N-(4-fluorobenzyl)-2-hydroxyphenylsulfonamido)methyl)benzoic acid (48 mg, 0.10 mol) in DMF, were added. N-(3,5-dichlorobenzyl)-1-(4-fluorophenyl)methanamine (28 mg, 0.1 mmol), HATU (48 mg, 0.15 mmol), and DIPEA (0.052 mL, 0.30 mmol). The reaction mixture was stirred at room temperature for 2 h and purified by preparative HPLC (Column YMC S5 ODS C18 20×100 mm; Solvent A=10% MeOH-90% H2O with 0.1% TFA; Solvent B=10% H2O-90% MeOH with 0.1% TFA). The desired fractions were combined, concentrated and lyophilized to give the title compound (40 mg, 51%) as a white solid. 1H NMR (CD3OD) δ 7.71 (d, 1H, J=2.5 Hz), 7.54 (d, 1H, J=2.5 Hz), 7.37-7.05 (m, 13H), 6.85 (t, 2H, J=8.8 Hz), 4.70 (br, 1H), 4.64 (br, 1H), 4.54 (s, 2H), 4.50 (s, 2H), 4.46 (br, 1H), 4.42 (br, 1H). MS (ESI): 750.8 (M+H)+.

Workup

  1. custompurified by preparative HPLC (Column YMC S5 ODS C18 20×100 mm; Solvent A=10% MeOH-90% H2O with 0.1% TFA; Solvent B=10% H2O-90% MeOH with 0.1% TFA)
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-c8006f78796b475fa1e9db1b2db5b5d0
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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