4-Methylmorpholine → HCID 137194580, compound

HRID 731341Notes

Reaction equation

HRID 731341 reaction equation
[CH3:1][N:2]([CH3:14])[NH:3][CH:4]1[CH2:8][CH2:7][CH2:6][CH:5]1[C:9]([O:11]CC)=O.[CH3:15][S:16]([NH:19][C:20]1[CH:35]=[CH:34][C:23]2[NH:24][C:25]([CH2:30][C:31](O)=[O:32])=[N:26][S:27](=[O:29])(=[O:28])[C:22]=2[CH:21]=1)(=[O:18])=[O:17].CN1CCOCC1.[ClH:43].CN(C)CCCN=C=NCC>CN(C)C=O>[ClH:43].[CH3:14][N:2]([CH3:1])[N:3]1[C@@H:4]2[C@@H:5]([CH2:6][CH2:7][CH2:8]2)[C:9]([OH:11])=[C:30]([C:25]2[NH:24][C:23]3[CH:34]=[CH:35][C:20]([NH:19][S:16]([CH3:15])(=[O:18])=[O:17])=[CH:21][C:22]=3[S:27](=[O:28])(=[O:29])[N:26]=2)[C:31]1=[O:32]

Participants

6

Reactant 4

HCID 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 57671202HCID 57671202, compound

Product 1

HCID 137194580HCID 137194580, compoundYield 52.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Ethyl 2-(2,2-dimethylhydrazinyl)cyclopentanecarboxylate (0.16 g, 0.82 mmol) was dissolved in anhydrous N,N-dimethylformamide (8 mL). (7-Methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 0.27 g, 0.82 mmol) was added followed by N-methylmorpholine (0.19 mL, 1.72 mmol). The mixture was stirred until everything dissolved, approximately 5 min. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.16 g, 0.86 mmol) was added and the mixture was stirred at 25° C. for 16 h. The reaction was quenched via addition of saturated aqueous sodium bicarbonate solution (20 mL). The mixture was extracted with ethyl acetate (3×30 mL). The organic layers were combined and washed with saturated aqueous brine solution (20 mL). The resulting solution was dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a golden oil. The residue was triturated with ethyl acetate to afford the desired product, cis-N-[3-(1-dimethylamino-4-hydroxy-2-oxo-2,4a,5,6,7,7a-hexahydro-1H-[1]pyrindin-3-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl]-methanesulfonamide hydrochloride (0.22 g, 0.43 mmol, 52%), as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 1.48-1.73 (2H, m), 1.88-2.20 (4H, m), 2.82 (6H, s), 3.06 (3H, s), 4.01 (1H, s), 7.49-7.74 (3H, m), 10.18 (1H, s). LC-MS (ESI) calcd for C18H23N5O6S2 469.54, found 470.2 [M+H+].

Workup

  1. dissolutiondissolved, approximately 5 min
  2. stirringthe mixture was stirred at 25° C. for 16 h
  3. customThe reaction was quenched via addition of saturated aqueous sodium bicarbonate solution (20 mL)
  4. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
  5. washwashed with saturated aqueous brine solution (20 mL)
  6. dry with materialThe resulting solution was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a golden oil
  10. customThe residue was triturated with ethyl acetate

Sources & evidence

ORD record
ord-68ce9b2280c140b8bce8bfb5b2afdab0
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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