Ethanol → HCID 136132920, compound

HRID 421507Notes

Reaction equation

HRID 421507 reaction equation
C(O[C:4](=[O:20])[C:5]([CH3:19])([CH2:11][NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:6][CH2:7][CH:8]([CH3:10])[CH3:9])C.[CH3:21][S:22]([NH:25][CH2:26][C:27]1[C:35]2[S:34](=[O:37])(=[O:36])[N:33]=[C:32]([CH2:38][C:39](O)=[O:40])[NH:31][C:30]=2[S:29][CH:28]=1)(=[O:24])=[O:23].Cl.CN(C)CCCN=C=NCC.[O-]CC.[Na+].C(O)C>CN(C)C=O>[OH:20][C:4]1[C:5]([CH3:19])([CH2:6][CH2:7][CH:8]([CH3:9])[CH3:10])[CH2:11][N:12]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:39](=[O:40])[C:38]=1[C:32]1[NH:31][C:30]2[S:29][CH:28]=[C:27]([CH2:26][NH:25][S:22]([CH3:21])(=[O:23])=[O:24])[C:35]=2[S:34](=[O:37])(=[O:36])[N:33]=1

Participants

7

Reactant 5

HCID 702EthanolHCID 2723922Sodium ethoxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57334723[7-(Methanesulfonylamino-methyl)-1,1-dioxo-1,4-dihydro-1lambda6 thieno[2,3-e][1,2,4]thiadiazin-3-yl]-acetic acidHCID 57455186HCID 57455186, compound

Product 1

HCID 136132920HCID 136132920, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

2,5-Dimethyl-2-phenylaminomethyl-hexanoic acid ethyl ester (0.10 g, 0.36 mmol) was dissolved in N,N-dimethylformamide (4 mL). [7-(Methanesulfonylamino-methyl)-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-acetic acid (prepared as described in Example 2c; 0.127 g, 0.36 mmol) was added followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.083 g, 0.43 mmol). The mixture was stirred at 25° C. for 5 h. The solvent was removed in vacuo then re-dissolved in ethanol. A 21 wt. % solution of sodium ethoxide in ethanol (806 μL, 2.16 mmol) was added to the mixture and stirred at 60° C. for 16 h. Upon cooling to 25° C., the mixture was concentrated in vacuo to afford a thick oil. The oil was partitioned between dichloromethane (4 mL) and 1.0 M aqueous hydrochloric acid solution (6 mL). The organic phase was loaded directly onto a prepacked RediSep silica gel column and purified by flash column chromatography (Teledyne Isco RediSep column; 20-100% ethyl acetate in hexanes) to afford the desired product, N-{3-[4-hydroxy-5-methyl-5-(3-methyl-butyl)-2-oxo-1-phenyl-1,2,5,6-tetrahydro-pyridin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-7-ylmethyl}-methanesulfonamide (0.079 g, 0.1401 mmol, 39%), as an off white powder. 1H NMR (400 MHz, Acetone-d6) δ: 0.90 (6H, d, J=8.0 Hz), 1.25-1.38 (2H, m), 1.49-1.59 (1H, m), 1.80-1.89 (2H, m), 2.08 (3H, s), 2.96 (3H, s), 3.78-3.85 (2H, m), 4.44 (2H, d, J=6.1 Hz), 6.42 (1H, t, J=6.3 Hz), 7.31-7.48 (6H, m). LC-MS (ESI) calculated for C24H30N4O6S3 566.13. found 567.2 [M+H+].

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthen re-dissolved in ethanol
  3. stirringstirred at 60° C. for 16 h
  4. temperatureUpon cooling to 25° C.
  5. concentrationthe mixture was concentrated in vacuo
  6. customto afford a thick oil
  7. customThe oil was partitioned between dichloromethane (4 mL) and 1.0 M aqueous hydrochloric acid solution (6 mL)
  8. custompurified by flash column chromatography (Teledyne Isco RediSep column; 20-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9f294e3092b143a7a25ab662cb6d3170
Source dataset
uspto-grants-2012_01
Patent number
US08097613B2

Reaction notes

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