Dicyclohexylcarbodiimide → cis-2-{(4-Fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid ethyl ester

HRID 731234Notes

Reaction equation

HRID 731234 reaction equation
[CH3:1][S:2]([NH:5][C:6]1[CH:21]=[CH:20][C:9]2[NH:10][C:11]([CH2:16][C:17]([OH:19])=O)=[N:12][S:13](=[O:15])(=[O:14])[C:8]=2[CH:7]=1)(=[O:4])=[O:3].[CH2:22]([O:24][C:25]([C@@H:27]1[CH2:31][CH2:30][CH2:29][C@@H:28]1[NH:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)=[O:26])[CH3:23].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[CH2:22]([O:24][C:25]([C@@H:27]1[CH2:31][CH2:30][CH2:29][C@@H:28]1[N:32]([CH2:33][C:34]1[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=1)[C:17](=[O:19])[CH2:16][C:11]1[NH:10][C:9]2[CH:20]=[CH:21][C:6]([NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[CH:7][C:8]=2[S:13](=[O:14])(=[O:15])[N:12]=1)=[O:26])[CH3:23]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 248585392H-1,2,4-Benzothiadiazine-3-acetic acid, 7-[(methylsulfonyl)amino]-, 1,1-dioxideHCID 25231427HCID 25231427, compound

Product 1

HCID 69059691cis-2-{(4-Fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid ethyl esterYield 28.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
25 °C

Procedure

To a solution of (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 0.140 g, 0.241 mmol) and cis-2-(4-fluoro-benzylamino)-cyclopentanecarboxylic acid ethyl ester (0.064 g, 0.241 mmol) in N,N-dimethylformamide (10 mL) was added a 2.0 M solution of N,N′-dicyclohexylcarbodiimide in N,N-dimethylformamide (121 μL, 0.241 mmol) and the reaction mixture was stirred at 25° C. for 16 h. The solvent was removed in vacuo and the residue was purified by flash column chromatography (Teledyne Isco RediSep Flash Column 4 g; 0-10% methanol in dichloromethane) to afford the desired product, cis-2-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid ethyl ester (0.04 g, 0.0689 mmol, 28.6%). LC-MS (ESI) calcd for C25H29FN4O7S2 580.15, found 581.2 [M+H+].

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by flash column chromatography (Teledyne Isco RediSep Flash Column 4 g; 0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-1d28cdde51854d8b9a87caf28821b4e0
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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