Hydrochloric Acid → HCID 177727099, compound

HRID 615807Notes

Reaction equation

HRID 615807 reaction equation
I[CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[CH:26]([NH:27][C:28](=[O:58])/[C:29](=[N:55]\[O:56][CH3:57])/[C:30]3[N:31]=[C:32]([NH:35]C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[S:33][CH:34]=3)[C:25](=[O:59])[N:7]2[C:8]=1[C:9]([O:11]C(C1C=CC=CC=1)C1C=CC=CC=1)=[O:10].[CH3:60][NH:61][C:62]1[S:63][C:64]2[CH:69]=[CH:68][N:67]=[CH:66][C:65]=2[N:70]=1.Cl>C1COCC1.C(O)=O.O>[NH2:35][C:32]1[S:33][CH:34]=[C:30](/[C:29](=[N:55]/[O:56][CH3:57])/[C:28]([NH:27][CH:26]2[C:25](=[O:59])[N:7]3[C:8]([C:9]([O-:11])=[O:10])=[C:3]([CH2:2][N+:67]4[CH:68]=[CH:69][C:64]5[S:63][C:62]([NH:61][CH3:60])=[N:70][C:65]=5[CH:66]=4)[CH2:4][S:5][C@H:6]23)=[O:58])[N:31]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 12329863N-Methyl[1,3]thiazolo[4,5-c]pyridin-2-amineHCID 13239634benzhydryl (6R)-3-(iodomethyl)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 177727099HCID 177727099, compoundYield 27.5%

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of AgClO4 (207 mg, 1.0 mmole) in THF (1 ml) was added in approximately four equal portions, during one hour, to a stirred solution at 25° C. of benzhydryl 3-iodomethyl-7-[(Z)-2-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate [VIIa] (913 mg, 1.0 mmole) and 2-methylaminothiazolo[4,5-c]pyridine (165 mg, 1.0 mmole) in THF (8 ml). Stirring was continued for an additional hour. The mixture was filtered through diatomaceous earth and the filtrate concentrated. A solution of the residue in CH2Cl2 was washed with dilute aqueous HCl and then with brine. The CH2Cl2 layer was dried over Na2SO4 and concentrated to leave the crude protected quaternized cephalosporin as a brown froth. Concentrated HCl (0.5 ml) was added to a stirred solution of the froth in 95-97% formic acid (15 ml) at 25° C. The solution was stirred for 50 minutes and then was diluted with H2O (20 ml). The resulting mixture was filtered and the filtrate concentrated on a rotary evaporator. The residue was suspended in H2O (20 ml), and the pH of the stirred mixture was adjusted to 5.1 with dilute NaOH. The mixture was filtered and the product isolated from the filtrate by high performance low pressure liquid chromatography (HPLPLC). The filtrate was applied to a glass column (300×22 mm) which was packed with Waters PrepPAK-500/C18. The column was eluted first with H2O and then with H2O-10% acetonitrile to elute the title compound. The appropriate fractions were combined and partially concentrated to remove the CH3CN. The aqueous solution was lyophilized to afford 154 mg of the title compound (Iy).

Workup

  1. waitwas continued for an additional hour
  2. filtrationThe mixture was filtered through diatomaceous earth
  3. concentrationthe filtrate concentrated
  4. washA solution of the residue in CH2Cl2 was washed with dilute aqueous HCl
  5. dry with materialThe CH2Cl2 layer was dried over Na2SO4
  6. concentrationconcentrated
  7. customto leave the crude
  8. stirringThe solution was stirred for 50 minutes
  9. filtrationThe resulting mixture was filtered
  10. concentrationthe filtrate concentrated on a rotary evaporator
  11. filtrationThe mixture was filtered
  12. customthe product isolated from the filtrate by high performance low pressure liquid chromatography (HPLPLC)
  13. washThe column was eluted first with H2O
  14. washwith H2O-10% acetonitrile to elute the title compound
  15. concentrationpartially concentrated
  16. customto remove the CH3CN

Sources & evidence

ORD record
ord-7edbf6a8d87e4883a947752fbc299ffb
Source dataset
uspto-grants-1985_02
Patent number
US04500526

Reaction notes

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