4-Methylmorpholine → HCID 135955714, compound

HRID 731334Notes

Reaction equation

HRID 731334 reaction equation
CO[C:3]([C@@H:5]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C@@H:6]1[NH:13][CH2:14][CH2:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:4].[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.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[CH3:19][C:16]([CH3:17])([CH3:18])[CH2:15][CH2:14][N:13]1[C:36](=[O:37])[C:35]([C:30]2[NH:29][C:28]3[CH:39]=[CH:40][C:25]([NH:24][S:21]([CH3:20])(=[O:23])=[O:22])=[CH:26][C:27]=3[S:32](=[O:34])(=[O:33])[N:31]=2)=[C:3]([OH:4])[CH:5]2[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH:6]12

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 248585392H-1,2,4-Benzothiadiazine-3-acetic acid, 7-[(methylsulfonyl)amino]-, 1,1-dioxideHCID 69062615HCID 69062615, compound

Product 1

HCID 135955714HCID 135955714, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

cis-2-(3,3-Dimethyl-butylamino)-cyclooctanecarboxylic acid methyl ester (0.18 g, 0.67 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, 0.23 g, 0.67 mmol) was added followed by N-methylmorpholine (0.15 mL, 1.40 mmol). The mixture was stirred until everything dissolved, approximately 5 min. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.13 g, 0.70 mmol) was added and the mixture was stirred at 25° C. for 4 h. Triethylamine (0.28 mL, 2.00 mmol) was added and the mixture was stirred at 50° C. for 16 h. Upon cooling to 25° C., the solution was diluted with ethyl acetate (50 mL) and washed with 1.0 M aqueous hydrochloric acid solution (2×50 mL), saturated aqueous brine solution (20 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a golden oil. Purification by flash column chromatography (Teledyne Isco RediSep Flash Column; 0-20% ethyl acetate in dichloromethane) afforded the desired product, N-{3-[1-(3,3-dimethyl-butyl)-4-hydroxy-2-oxo-1,2,4a,5,6,7,8,9,10,10a-decahydro-cycloocta[b]pyridin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (0.18 g, 0.32 mmol, 48%), as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 1.02 (9H, s), 1.42-2.21 (14H, m), 2.80-2.86 (1H, m), 3.06 (3H, s), 3.11-3.15 (1H, m), 3.66-3.70 (1H, m), 3.99-4.04 (1H, m), 6.57 (1H, s), 7.22-7.26 (1H, m), 7.60-7.66 (2H, m). LC-MS (ESI) calcd for C25H36N4O6S2 552.71, found 553.3 [M+H+].

Workup

  1. dissolutiondissolved, approximately 5 min
  2. stirringthe mixture was stirred at 25° C. for 4 h
  3. stirringthe mixture was stirred at 50° C. for 16 h
  4. washwashed with 1.0 M aqueous hydrochloric acid solution (2×50 mL), saturated aqueous brine solution (20 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a golden oil
  9. customPurification by flash column chromatography (Teledyne Isco RediSep Flash Column; 0-20% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-610a02184a874df3829f25bef065dc99
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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