Lithium hydroxide, monohydrate → HCID 11713302, compound

HRID 852001Notes

Reaction equation

HRID 852001 reaction equation
CO[C:3](=[O:33])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]([S:23]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[CH:12]2[CH2:18][CH:17]([CH:19]([CH3:21])[CH3:20])[CH2:16][CH2:15][NH:14][C:13]2=[O:22])=[CH:6][CH:5]=1.O[Li].O.O[NH:38][C:39](=[NH:41])[CH3:40].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.O>[Cl:32][C:29]1[CH:28]=[CH:27][C:26]([S:23]([N:11]([CH:12]2[CH2:18][CH:17]([CH:19]([CH3:20])[CH3:21])[CH2:16][CH2:15][NH:14][C:13]2=[O:22])[CH2:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]3[O:33][N:41]=[C:39]([CH3:40])[N:38]=3)=[CH:5][CH:6]=2)(=[O:25])=[O:24])=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 168937Lithium hydroxide, monohydrateHCID 2724141Tetrabutylammonium FluorideHCID 11496884HCID 11496884, compoundHCID 178465666HCID 178465666, compound2×

Product 1

HCID 11713302HCID 11713302, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

4-{[(4-Chloro-benzenesulfonyl)-(5-isopropyl-2-oxo-azepan-3-yl)-amino]-methyl}-benzoic acid methyl ester (0.30 g, 0.60 mmol) was saponified to the acid using LiOH.H2O (0.04 g, 0.90 mmol). The acid (0.10 g, 0.21 mmol) was dissolved in THF (3 ml) and added dropwise to a solution of 1,1-carbonyl diimidazole (CDI, 0.04 g, 0.23 mmol) in THF (0.5 ml). After 30 min, N-hydroxy-acetamidine (0.04 g, 0.23 mmol) was added. A further two equivalents each of CDI and N-hydroxy-acetamidine were added during a further 48 h stirring at r.t. The reaction mixture was concentrated and crude, coupled amidine was purified over silica gel (gradient ethyl acetate to ethyl acetate/methanol 15%): white solid 0.09 g (73%); MS: m/e=535.5 (MH+). Purified amidine (0.08 g, 0.15 mmol) cyclised in the presence of tetrabutylammonium fluoride (1 M, THF 5 ml) over 36 h at r.t. The reaction mixture was diluted with water and extracted with ethyl acetate (3×). The combined organice extracts were washed with water, brine, dried (MgSO4), filtered and concentrated under reduced pressure. The concentrated, crude product was purified using preparative RP(C18) chromatography: lyophilisate 15 mg; MS: m/e=517.4 (MH+).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customwas purified over silica gel (gradient ethyl acetate to ethyl acetate/methanol 15%)
  3. extractionextracted with ethyl acetate (3×)
  4. washThe combined organice extracts were washed with water, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe concentrated, crude product was purified

Sources & evidence

ORD record
ord-ebfbf359d8d04b49a1ef335e97efcdfc
Source dataset
uspto-grants-2007_08
Patent number
US07253158B2

Reaction notes

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