Hydrochloric Acid → HCID 135949487, compound

HRID 1172396Notes

Reaction equation

HRID 1172396 reaction equation
C(O[C:4](=[O:17])[C:5]([CH3:16])([CH:11]1[CH2:15][CH2:14][CH2:13][NH:12]1)[CH2:6][CH2:7][CH:8]([CH3:10])[CH3:9])C.[CH3:18][S:19]([NH:22][C:23]1[CH:38]=[CH:37][C:26]2[NH:27][C:28]([CH2:33][C:34](O)=[O:35])=[N:29][S:30](=[O:32])(=[O:31])[C:25]=2[CH:24]=1)(=[O:21])=[O:20].Cl.CN(C)CCCN=C=NCC.CN1CCOCC1.[H-].[Na+].Cl>CN(C)C=O>[OH:17][C:4]1[C:5]([CH3:16])([CH2:6][CH2:7][CH:8]([CH3:9])[CH3:10])[CH:11]2[N:12]([CH2:13][CH2:14][CH2:15]2)[C:34](=[O:35])[C:33]=1[C:28]1[NH:27][C:26]2[CH:37]=[CH:38][C:23]([NH:22][S:19]([CH3:18])(=[O:21])=[O:20])=[CH:24][C:25]=2[S:30](=[O:32])(=[O:31])[N:29]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 24758Sodium hydrideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 248585392H-1,2,4-Benzothiadiazine-3-acetic acid, 7-[(methylsulfonyl)amino]-, 1,1-dioxideHCID 57446166HCID 57446166, compound

Product 1

HCID 135949487HCID 135949487, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2,5-dimethyl-2-pyrrolidin-2-yl-hexanoic acid ethyl ester (266 mg, 1.1 mmol), (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (367 mg, 1.1 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (274 mg, 1.43 mmol) in N,N-dimethylformamide (8 mL) was treated with N-methylmorpholine (289 mg, 2.86 mmol) and stirred for 1 h. The reaction was quenched with 1.0 M aqueous hydrochloric acid solution, extracted with ethyl acetate, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude oil was dissolved in ethanol, treated with a 60% oil dispersion of sodium hydride (176 mg, 7.33 mmol) and heated to a vigorous reflux for 48 h. Upon cooling to 25° C., the reaction mixture was over ice in a 1.0 M aqueous hydrochloride solution. The resulting precipitate was collected by vacuum filtration to afford the crude product as a tan solid. The crude residue was purified by prep-HPLC to afford two separate diastereomers of the desired product, N-{3-[7-hydroxy-8-methyl-8-(3-methyl-butyl)-5-oxo-1,2,3,5,8,8a-hexahydro-indolizin-6-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide, as tan solids. Assignment of the relative or absolute configuration of the stereocenters was not attempted. Diasteromer 1 (122 mg, 22%): 1H NMR (400 MHz, CD2Cl2) δ: 0.84-0.90 (6H, m), 1.27 (3H, s), 1.84-2.20 (2H, m), 3.07 (3H, s), 3.50-3.58 (1H, m), 3.64-3.70 (1H, m), 3.90-3.95 (1H, m), 5.34 (2H, d, J=1.6 Hz), 6.83 (1H, s), 7.25-7.28 (1H, m), 7.54-7.58 (1H, m), 7.66-7.68 (1H, m), 14.22 (1H, s). LC-MS (ESI) calcd for C22H30N4O6S2 510.16, found 511.4 [M+H+]. Diasteromer 2 (67 mg, 12%): 1H NMR (400 MHz, CD2Cl2) δ: 0.93-0.97 (6H, m), 1.14 (2H, s), 1.22-1.45 (3H, m), 1.52-1.60 (1H, m), 1.83-2.19 (5H, m), 3.06 (3H, s), 3.42-3.59 (1H, m), 3.76-3.96 (2H, m), 5.34 (1H, s), 6.93-6.94 (1H, m), 7.27 (1H, d, J=8.8 Hz), 7.56-7.59 (1H, m), 7.66-7.69 (1H, m), 14.30 (1H, bs), 15.27 (1H, s). LC-MS (ESI) calcd for C22H30N4O6S2 510.16, found 511.4 [M+H+].

Workup

  1. customThe reaction was quenched with 1.0 M aqueous hydrochloric acid solution
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe crude oil was dissolved in ethanol
  7. temperatureheated to
  8. temperaturea vigorous reflux for 48 h
  9. filtrationThe resulting precipitate was collected by vacuum filtration

Sources & evidence

ORD record
ord-b7234c0c5810401c91d6237b16c86ecb
Source dataset
uspto-grants-2010_11
Patent number
US07834009B2

Reaction notes

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