Hydrochloric Acid → N-[3-[(4aR,7aS)-1-[(4-fluoro-3-methyl-phenyl)methyl]-4-hydroxy-2-oxo-5,6,7,7a-tetrahydro-4aH-cyclopenta[b]pyridin-3-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamide

HRID 731299Notes

Reaction equation

HRID 731299 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][NH:7][C@H:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[C:13]([O:15]C)=O)=[CH:4][C:3]=1[CH3:19].[CH3:20][S:21]([NH:24][C:25]1[CH:40]=[CH:39][C:28]2[NH:29][C:30]([CH2:35][C:36](O)=[O:37])=[N:31][S:32](=[O:34])(=[O:33])[C:27]=2[CH:26]=1)(=[O:23])=[O:22].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.Cl>CN(C)C=O>[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[C@@H:8]3[C@@H:9]([CH2:10][CH2:11][CH2:12]3)[C:13]([OH:15])=[C:35]([C:30]3[NH:29][C:28]4[CH:39]=[CH:40][C:25]([NH:24][S:21]([CH3:20])(=[O:23])=[O:22])=[CH:26][C:27]=4[S:32](=[O:33])(=[O:34])[N:31]=3)[C:36]2=[O:37])=[CH:4][C:3]=1[CH3:19]

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 57671233HCID 57671233, compound

Product 1

HCID 135955950N-[3-[(4aR,7aS)-1-[(4-fluoro-3-methyl-phenyl)methyl]-4-hydroxy-2-oxo-5,6,7,7a-tetrahydro-4aH-cyclopenta[b]pyridin-3-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a stirred solution of methyl (1R,2S)-2-[(4-fluoro-3-methylbenzyl)amino]cyclopentanecarboxylate (120 mg, 0.45 mmol) and (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 150 mg, 0.45 mmol) in anhydrous N,N-dimethylformamide (4 mL) under a nitrogen atmosphere, N-methylmorpholine (0.15 mL, 1.40 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (86 mg, 0.45 mmol) were added sequentially. The mixture was stirred at 25° C. for 2.5 h, and then poured into 1.0 M aqueous hydrochloric acid solution and extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous brine solution, dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo to afford the amide intermediate, which was used directly in the next step without further purification.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layers were washed with saturated aqueous brine solution
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-0519a3c7d7c943bda017bb66694576e3
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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