Sodium ethoxide → HCID 137194588, compound

HRID 731381Notes

Reaction equation

HRID 731381 reaction equation
C([O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[N:11]([CH:32]([CH3:34])[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>[OH:3][C:4]1[C@H:6]2[C@H:7]([CH2:8][CH2:9][CH2:10]2)[N:11]([CH:32]([CH3:34])[CH3:33])[C:12](=[O:31])[C:13]=1[C:14]1[NH:19][C:18]2[CH:20]=[CH:21][C:22]([NH:24][S:25]([CH3:28])(=[O:26])=[O:27])=[CH:23][C:17]=2[S:16](=[O:29])(=[O:30])[N:15]=1

Participants

4

Reactant 2

HCID 2723922Sodium ethoxideHCID 57671254HCID 57671254, compound

Product 1

HCID 137194588HCID 137194588, compoundYield 33.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of the crude 2-{isopropyl-[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-(4-hydroxy-1-isopropyl-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 (77.6 mg, 0.166 mmol, 33.2% over two steps), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.10-1.32 (6H, m), 1.46-2.13 (7H, m), 2.28 (1H, bs), 3.06 (3H, s), 3.95 (1H, bs), 4.54-5.10 (1H, m), 7.49-7.63 (3H, m), 10.17 (1H, s). LC-MS (ESI) calcd for C19H24N4O6S2 468.11, found 469.3 [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-04d5562754bd4c1590c0194c695fc9bc
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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