Hydrochloric Acid → N-[3-[(4aR,7aS)-4-hydroxy-1-isopentyl-2-oxo-5,6,7,7a-tetrahydro-4aH-cyclopenta[b]pyridin-3-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamide

HRID 731318Notes

Reaction equation

HRID 731318 reaction equation
C([O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@@H:7]1[N:11]([C:17](=[O:36])[CH2:18][C:19]1[NH:24][C:23]2[CH:25]=[CH:26][C:27]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])=[CH:28][C:22]=2[S:21](=[O:35])(=[O:34])[N:20]=1)[CH2:12][CH2:13][CH:14]([CH3:16])[CH3:15])=O)C.[O-]CC.[Na+].Cl>C(O)C>[OH:3][C:4]1[C@H:6]2[C@H:7]([CH2:8][CH2:9][CH2:10]2)[N:11]([CH2:12][CH2:13][CH:14]([CH3:15])[CH3:16])[C:17](=[O:36])[C:18]=1[C:19]1[NH:24][C:23]2[CH:25]=[CH:26][C:27]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])=[CH:28][C:22]=2[S:21](=[O:35])(=[O:34])[N:20]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 57671209HCID 57671209, compound

Product 1

HCID 135955690N-[3-[(4aR,7aS)-4-hydroxy-1-isopentyl-2-oxo-5,6,7,7a-tetrahydro-4aH-cyclopenta[b]pyridin-3-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamideYield 36.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

(1R,2S)-2-[[2-(7-Methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-(3-methyl-butyl)-amino]-cyclopentanecarboxylic acid ethyl ester (0.3 mmol) was dissolved in ethanol (3 mL), a 21% w/w solution of sodium ethoxide in ethanol (0.56 mL, 1.5 mmol) was added into the above solution. The mixture was stirred at 60° C. for 2 h and allowed to cool to 25° C. The mixture was poured into 0.5 M aqueous hydrochloric acid solution (50 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo to afford the crude product, which was purified by flash column chromatography (Teledyne Isco RediSep Column; 100% ethyl acetate in hexanes) to afford the desired product, (4aR,7aS)-N-{3-[4-hydroxy-1-(3-methyl-butyl)-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 (0.054 g, 0.109 mmol, 36.3% over two steps), as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 0.93 (6H, d, J=6.1 Hz), 1.35-1.65 (7H, m), 2.06-2.18 (2H, m), 3.06 (3H, s), 3.17-3.34 (3H, m), 3.65-3.73 (1H, m), 3.92 (1H, bs), 7.49-7.56 (3H, m), 10.16 (1H, bs). LC-MS (ESI) calcd for C21H28N4O6S2 496.15, found 497.4 [M+H+].

Workup

  1. temperatureto cool to 25° C
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customto afford the crude product, which
  6. customwas purified by flash column chromatography (Teledyne Isco RediSep Column; 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c9b9b82adf914c75bc49eae08bb9d54f
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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