Triethylamine → methyl (1aRS,7bSR)-5-{2-[((S)-1-ethylpyrrolidin-3-ylcarbamoyl)methyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

HRID 927966Notes

Reaction equation

HRID 927966 reaction equation
[C:1]([CH2:4][C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=1[S:12]([NH:15][C:16]1[C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]2[C:19]([CH:20]3[CH2:30][CH:21]3[CH2:22][O:23]2)=[CH:18][CH:17]=1)(=[O:14])=[O:13])(O)=[O:2].CCN=C=[N:35][CH2:36][CH2:37][CH2:38][N:39]([CH3:41])[CH3:40].[CH2:42](N(CC)CC)C>C(Cl)Cl>[CH2:41]([N:39]1[CH2:38][CH2:37][C@H:36]([NH:35][C:1]([CH2:4][C:5]2[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=2[S:12]([NH:15][C:16]2[C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]3[C:19]([CH:20]4[CH2:30][CH:21]4[CH2:22][O:23]3)=[CH:18][CH:17]=2)(=[O:13])=[O:14])=[O:2])[CH2:40]1)[CH3:42]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 71006995methyl (1aRS,7bSR)-5-(2-carboxymethyl-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 71006907methyl (1aRS,7bSR)-5-{2-[((S)-1-ethylpyrrolidin-3-ylcarbamoyl)methyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylateYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl (1aRS,7bSR)-5-(2-carboxymethyl-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 83, 0.180 g), (S)-1-ethylpyrrolidin-3-ylamine ditrifluoroacetic acid salt (Intermediate 81, 0.171 g), EDAC (0.144 g) and triethylamine (0.202 g) in DCM (5 mL) was allowed to stand at room temperature for 6 days then washed with water and filtered through a phase separator. The filtrate was directly purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-20% to give methyl (1aRS,7bSR)-5-{2-[((S)-1-ethylpyrrolidin-3-ylcarbamoyl)methyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.178 g) as an off-white foam.

Workup

  1. washthen washed with water
  2. filtrationfiltered through a phase separator
  3. customThe filtrate was directly purified by chromatography on silica
  4. washeluting with a mixture of methanol and DCM with a gradient of 0-20%

Sources & evidence

ORD record
ord-e261c671c7074902a93a415ed614954c
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

Loading…