Tetrahydrofuran → 3-{2-(3-Chloro-5-fluorophenyl)-5-[(4-oxoimidazolidin-1-yl)carbonyl]thiophen-3-yl}benzenecarbonitrile

HRID 1036997Notes

Reaction equation

HRID 1036997 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[S:13][C:12]([C:14]([OH:16])=O)=[CH:11][C:10]=2[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[N:24])[CH:18]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.C1CN([P+](ON2N=[N:49][C:44]3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C([N:61](CC)C(C)C)(C)C.[O:67]1CC[CH2:69][CH2:68]1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[S:13][C:12]([C:14]([N:61]3[CH2:69][C:68](=[O:67])[NH:49][CH2:44]3)=[O:16])=[CH:11][C:10]=2[C:17]2[CH:18]=[C:19]([C:23]#[N:24])[CH:20]=[CH:21][CH:22]=2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 580667575-(3-Chloro-5-fluorophenyl)-4-(3-cyanophenyl)thiophene-2-carboxylic acid

Product 1

HCID 468335003-{2-(3-Chloro-5-fluorophenyl)-5-[(4-oxoimidazolidin-1-yl)carbonyl]thiophen-3-yl}benzenecarbonitrile

Procedure

40.5 mg of the compound from Example 19A having a purity of 76% (0.08 mmol), 24.9 mg (0.13 mmol) of the compound from Example 4A and 88.4 mg (0.17 mmol) of PyBOP are provided in 2 ml of tetrahydrofuran, and 0.04 ml (0.24 mmol) of N,N-diisopropylethylamine are added at room temperature. The reaction mixture is stirred at room temperature overnight and subsequently purified by preparative HPLC (RP18 column; eluent: acetonitrile/water gradient with addition of 0.1% formic acid). 16.8 mg (46% of theory) of the title compound are obtained.

Workup

  1. customsubsequently purified by preparative HPLC (RP18 column; eluent: acetonitrile/water gradient with addition of 0.1% formic acid)

Sources & evidence

ORD record
ord-5e56819666ec47f783d1996f89ab734c
Source dataset
uspto-grants-2013_10
Patent number
US08546438B2

Reaction notes

Loading…