Hydrochloric Acid → (1R,2S)-2-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4] thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid methyl ester

HRID 731271Notes

Reaction equation

HRID 731271 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].[CH3:22][O:23][C:24]([C@@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@@H:27]1[NH:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)=[O:25].Cl.CN(C)CCCN=C=NCC.CN1CCOCC1.Cl>CN(C)C=O>[CH3:22][O:23][C:24]([C@@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@@H:27]1[N:32]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=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:25]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 248585392H-1,2,4-Benzothiadiazine-3-acetic acid, 7-[(methylsulfonyl)amino]-, 1,1-dioxideHCID 57671242HCID 57671242, compound

Product 1

HCID 57671232(1R,2S)-2-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4] thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid methyl esterYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

(7-Methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 0.1 g, 0.3 mmol) was dissolved in anhydrous N,N-dimethylformamide (4 mL). (1R,2S)-2-(4-Fluoro-benzylamino)-cyclohexanecarboxylic acid methyl ester (0.79 g, 0.3 mmol) was added followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.06 g, 0.315 mmol). Then N-methylmorpholine (0.07 mL, 0.63 mmol) was added into the above reaction mixture. The mixture was stirred at 25° C. for 2 h. The solution was poured into 1.0 M aqueous hydrochloric acid solution (50 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford the crude product, (1R,2S)-2-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid methyl ester (0.3 mmol), as a yellow oil. LC-MS (ESI) calcd for C25H29FN4O7S2 580.15, found 581.3 [M+H+].

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a4c8274966ad4d37b6a3de572312098d
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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