Sodium ethoxide → HCID 137194587, compound

HRID 731377Notes

Reaction equation

HRID 731377 reaction equation
C([O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[N:11]([CH2:32][CH3:33])[C:12](=[O:31])[CH2:13][C:14]1[NH:19][C:18]2[CH:20]=[CH:21][C:22]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][C:17]=2[S:16](=[O:30])(=[O:29])[N:15]=1)=O)C.[O-]CC.[Na+]>C(O)C>[CH2:32]([N:11]1[C@@H:7]2[C@@H:6]([CH2:10][CH2:9][CH2:8]2)[C:4]([OH:3])=[C:13]([C:14]2[NH:19][C:18]3[CH:20]=[CH:21][C:22]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][C:17]=3[S:16](=[O:29])(=[O:30])[N:15]=2)[C:12]1=[O:31])[CH3:33]

Participants

4

Reactant 2

HCID 2723922Sodium ethoxideHCID 57671257HCID 57671257, compound

Product 1

HCID 137194587HCID 137194587, compoundYield 23.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of the crude 2-{ethyl-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclopentanecarboxylic acid ethyl ester in ethanol (20 mL) was treated with a 21% w/w solution of sodium ethoxide in ethanol (0.648 g) and stirred for 16 h at 60° C. Upon cooling, the reaction mixture was then quenched with 1.0 M aqueous hydrochloric acid solution (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered, and dried in vacuo. The residue was purified by prep-HPLC [Column ODS-A 5μ 100 Å, 150×21.2 mm, 5 micron, 50%-100% in 13.5 min @ 22 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water] to afford the desired product, cis-N-[3-(1-ethyl-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 (54.3 mg, 0.120 mmol, 23.9% over two steps), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.08-1.30 (3H, m), 1.48-1.70 (4H, m), 1.99-2.24 (3H, m), 3.05 (3H, s), 3.64 (1H, bs), 3.87-4.45 (2H, m), 7.49-7.60 (3H, m), 10.16 (1H, s). LC-MS (ESI) calcd for C18H22N4O6S2 454.10, found 455.2 [M+H+].

Workup

  1. temperatureUpon cooling
  2. customthe reaction mixture was then quenched with 1.0 M aqueous hydrochloric acid solution (20 mL)
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customdried in vacuo
  8. customThe residue was purified by prep-HPLC [Column ODS-A 5μ 100 Å, 150×21.2 mm, 5 micron, 50%-100% in 13.5 min @ 22 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water]

Sources & evidence

ORD record
ord-36086c8a3b2d473a9b059df139217b46
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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