Hydrochloric Acid → HCID 135955931, compound

HRID 731279Notes

Reaction equation

HRID 731279 reaction equation
CO[C:3]([CH:5]1[CH2:10][CH2:9][CH:8]=[CH:7][CH:6]1[NH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)=[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.[O-]CC.[Na+].Cl>CN(C)C=O.C(OCC)(=O)C.C(O)C>[F:19][C:16]1[CH:15]=[CH:14][C:13]([CH2:12][N:11]2[CH:6]3[CH:5]([CH2:10][CH2:9][CH:8]=[CH:7]3)[C:3]([OH:4])=[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:18][CH:17]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 2723922Sodium ethoxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 248585392H-1,2,4-Benzothiadiazine-3-acetic acid, 7-[(methylsulfonyl)amino]-, 1,1-dioxideHCID 57671185HCID 57671185, compound

Product 1

HCID 135955931HCID 135955931, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

2-(4-Fluoro-benzylamino)-cyclohex-3-enecarboxylic acid methyl ester (0.051 g, 0.19 mmol) was dissolved in anhydrous N,N-dimethylformamide (2 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, 0.065 g, 0.19 mmol) was added followed by N-methylmorpholine (0.05 mL, 0.43 mmol). The mixture was stirred until everything dissolved, approximately 5 min. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.041 g, 0.21 mmol) was added and the mixture was stirred at 25° C. for 3 h. The solution was diluted with ethyl acetate (25 mL) and washed with 1.0 M aqueous hydrochloric acid solution (2×25 mL), saturated aqueous brine solution (10 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a golden oil. The oil was dissolved in ethanol (4 mL) and a 21% w/w solution of sodium ethoxide in ethanol (0.3 mL, 0.8 mmol) was added, and the reaction mixture was heated to 60° C. for 2 h. Upon cooling to 25° C., the reaction mixture was acidified to pH 2-3 with 2.0 M aqueous hydrochloric acid solution, upon which the product precipitated while stirring. The solid was collected by vacuum filtration and purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 50×21.2 mm, 5 micron, 30%-95% in 9 min @ 30 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water] to afford the desired product, N-{3-[1-(4-fluoro-benzyl)-4-hydroxy-2-oxo-1,2,4a,5,6,8a-hexahydro-quinolin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (0.025 g, 0.046 mmol, 25%), as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 1.65-2.24 (4H, m), 3.04 (3H, s), 4.10-4.21 (1H, m), 5.01 (1H, d, J=16.0 Hz), 5.45 (1H, d, J=10.0 Hz), 5.86 (1H, d, J=8.8 Hz), 7.16 (2H, dd, J=8.8 Hz), 7.42 (2H, m), 7.51 (1H, m), 7.57 (12H, m), 10.20 (1H, s). LC-MS (ESI) calcd for C24H23FN4O6S2 546.10, found 547.3 [M+H+].

Workup

  1. dissolutiondissolved, approximately 5 min
  2. stirringthe mixture was stirred at 25° C. for 3 h
  3. washwashed with 1.0 M aqueous hydrochloric acid solution (2×25 mL), saturated aqueous brine solution (10 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a golden oil
  8. temperatureUpon cooling to 25° C.
  9. customprecipitated
  10. stirringwhile stirring
  11. filtrationThe solid was collected by vacuum filtration
  12. custompurified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 50×21.2 mm, 5 micron, 30%-95% in 9 min

Sources & evidence

ORD record
ord-dcd49668e6d74a279db0a44ce231ceee
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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