Hydrochloric Acid → HCID 135955793, compound

HRID 731368Notes

Reaction equation

HRID 731368 reaction equation
C([O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[N:11]([C:20](=[O:34])[CH2:21][C:22]1[NH:27][C:26]2[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=2[S:24](=[O:33])(=[O:32])[N:23]=1)[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)=O)C.[O-]CC.[Na+].Cl>C(O)C>[O:32]=[S:24]1(=[O:33])[C:25]2[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=2[NH:27][C:22]([C:21]2[C:20](=[O:34])[N:11]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[CH:7]3[CH:6]([C:4]=2[OH:3])[CH2:10][CH2:9][CH2:8]3)=[N:23]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 57671235HCID 57671235, compound

Product 1

HCID 135955793HCID 135955793, compoundYield 51.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

The crude 2-[[2-(1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-(4-fluoro-benzyl)-amino]-cyclopentanecarboxylic acid ethyl ester (0.503 mmol) was dissolved in ethanol (4 mL). A 21% w/w solution of sodium ethoxide in ethanol (1.8 mL) was added and the resulting reaction mixture was shaken for 16 h. A 1.0 M aqueous hydrochloric acid solution (9 mL) was added and the mixture was extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to afford the crude product, which was further purified by flash chromatography (Teledyne Isco RediSep Column; 0-100% ethyl acetate in hexanes) to afford the desired product, 3-(1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-1-(4-fluoro-benzyl)-4-hydroxy-1,4a,5,6,7,7a-hexahydro-[1]pyrindin-2-one (114.2 mg, 0.259 mmol, 51.5% over two steps), as an off-white solid. LC-MS (ESI) calcd for C22H20FN3O4S 441.12, found 442.4 [M+H+]. The 1H NMR spectrum indicated a 4:1 mixture of cis- and trans-isomers. 1H NMR (CDCl3, 400 MHz): δ 1.54-1.77 (m, 3H), 1.87-2.13 (m, 2H), 2.26-2.34 (m, 1H, 80%), 2.36-2.49 (m, 1H, 20%), 2.88-2.93 (m, 1H, 20%), 3.11-3.16 (m. 1H, 80%), 3.69-3.77 (m, 1H), 4.30 (d, 1H, 80%, J=14.8 Hz), 4.43 (d, 1H, 20%, J=14.8 Hz), 5.00 (d, 1H, 20%, J=14.8 Hz), 5.09 (d, 1H, 80%, J=15.2 Hz), 7.03-7.10 (m, 2H), 7.17-7.35 (m, 3H), 7.36-7.42 (m, 1H), 7.55-7.60 (m, 1H), 7.91-7.95 (m, 1H). Anal. calcd for C22H20FN3O4S H2O: C, 57.50; H, 4.83; N, 9.15; found: C, 57.54; H, 4.53; N, 8.79.

Workup

  1. customthe resulting reaction mixture
  2. extractionthe mixture was extracted with ethyl acetate (3×20 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford the crude product, which
  7. customwas further purified by flash chromatography (Teledyne Isco RediSep Column; 0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-b5c1899b6d924cc9bfbe6e420d7ed1c2
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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