N-Hydroxysuccinimide → (6R-trans)-1-chloro-N-[2-chloro-4-fluoro-5-(tetrahydro-6-hydroxy-1,3-dioxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)phenyl]methanesulfonamide

HRID 1107251

Reaction equation

HRID 1107251 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][S:9]([CH2:12][Cl:13])(=[O:11])=[O:10])=[CH:6][C:5]([NH:14][C:15]([N:17]2[CH2:21][C@H:20]([OH:22])[CH2:19][C@@H:18]2[C:23](O)=[O:24])=[O:16])=[C:4]([F:26])[CH:3]=1.ON1C(=O)CCC1=O>C(#N)C>[Cl:13][CH2:12][S:9]([NH:8][C:7]1[CH:6]=[C:5]([N:14]2[C:23](=[O:24])[C@H:18]3[CH2:19][C@@H:20]([OH:22])[CH2:21][N:17]3[C:15]2=[O:16])[C:4]([F:26])=[CH:3][C:2]=1[Cl:1])(=[O:11])=[O:10]

Participants

4

Reactant 2

HCID 80170N-HydroxysuccinimideHCID 53809153(2R-cis)-1-[[[4-chloro-5-[[(chloromethyl)sulfonyl]amino]-2-fluorophenyl]amino]carbonyl]4-hydroxy-2-pyrrolidinecarboxylic acid

Product 1

HCID 10982513(6R-trans)-1-chloro-N-[2-chloro-4-fluoro-5-(tetrahydro-6-hydroxy-1,3-dioxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)phenyl]methanesulfonamideYield 116.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a stirred solution of the title compound of Step F (2.7 g, 5.4 mmol) and N-hydroxysuccinimide (0.621 g, 5.4 mmol) in acetonitrile (50 mL) was added a solution of N,N-dicyclohexylcarbodiimide (1.14 g, 5.4 mmol) in acetonitrile (30 mL) over 30 minutes at 0 to -5° C. The reaction was stirred at room temperature for 14 h. The by-products were removed by filtration and the solvent was evaporated under reduced pressure to yield the title compound of Step G (2.6 g, quantitative yield) as a crude product melting at 198-200° C. 1H NMR (Me2SO-d6) δ 10.2 (br s, 1H), 7.8-7.7 (d, 1H), 7.5-7.4 (d, 1H), 5.2-5.1 (br s, 1H), 5.1-5.0 (s, 2H), 4.5 (m, 1H), 4.34.2 (m, 1H), 3.1 (m, 1H), 2.3 (m, 1H), 2.0 (m, 1H).

Workup

  1. customThe by-products were removed by filtration
  2. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-9cdfc9e65a3f467487ae38e5b3b3f0f4
Source dataset
uspto-grants-2000_05
Patent number
US06060432

Linked notes

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