Methanesulfonyl chloride → HCID 53765200, compound

HRID 1583870Notes

Reaction equation

HRID 1583870 reaction equation
[C:1]([NH2:9])(=[S:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[CH:10]([O:23][C:24]([C:26]1[N:27]2[CH:30]([S:31][CH2:32][C:33]=1[CH:34](Br)[CH:35]=O)[CH:29]([NH:38][C:39](=[O:69])[C:40](=[N:66][O:67][CH3:68])[C:41]1[N:42]=[C:43]([NH:46][C:47]([C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=3)([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[S:44][CH:45]=1)[C:28]2=[O:70])=[O:25])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CS(Cl)(=O)=O.C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C.C(N(CC)CC)C.N1C=CC=CC=1>[CH:10]([O:23][C:24]([C:26]1[N:27]2[CH:30]([S:31][CH2:32][C:33]=1[C:34]1[S:8][C:1]([C:2]3[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=3)=[N:9][CH:35]=1)[CH:29]([NH:38][C:39](=[O:69])[C:40](=[N:66][O:67][CH3:68])[C:41]1[N:42]=[C:43]([NH:46][C:47]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)([C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=3)[C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=3)[S:44][CH:45]=1)[C:28]2=[O:70])=[O:25])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

9

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 737155ThionicotinamideHCID 53742476HCID 53742476, compound

Product 1

HCID 53765200HCID 53765200, compound

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Thionicotinamide (0.28 g) and pyridine (0.16 g) are added to a solution of the syn isomer of 2-benzhydryloxycarbonyl-3-(1-bromo-2-oxoethyl)-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (mixture of the two diastereoisomers) (1.66 g) in tetrahydrofuran (20 cc) and the mixture is heated at 50° C. for 90 minutes. The reaction mixture is subsequently cooled to 0° C. and then treated successively with methanesulphonyl chloride (0.23 g) and triethylamine (0.56 cc). After 30 minutes at 0° C., the reaction mixture is poured into a mixture of a saturated solution of sodium bicarbonate (200 cc) and ethyl acetate (100 cc); the organic phase is decanted, washed with distilled water (150 cc) and with a saturated solution of sodium chloride (150 cc) and then dried over magnesium sulphate. The residue obtained after evaporation of the solvent to dryness under reduced pressure (4 kPa) at 40° C. is chromatographed on a column (height: 30 cm, diameter: 1.5 cm) containing silica gel (0.04-0.06 mm), elution being carried out under a pressure of 0.5 bar (50 kPa) with a mixture of cyclohexane and ethyl acetate (30/70 by volume) and 50 cc fractions being collected. Fractions 18 to 26 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. to give the syn isomer of 2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-3-[2-(pyridin-3-yl)-thiazol-5-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene (0.18 g) in the form of a beige powder.

Workup

  1. temperatureThe reaction mixture is subsequently cooled to 0° C.
  2. customthe organic phase is decanted
  3. washwashed with distilled water (150 cc) and with a saturated solution of sodium chloride (150 cc)
  4. dry with materialdried over magnesium sulphate
  5. customThe residue obtained
  6. customafter evaporation of the solvent to dryness under reduced pressure (4 kPa) at 40° C.
  7. customis chromatographed on a column (height: 30 cm, diameter: 1.5 cm)
  8. additioncontaining
  9. washsilica gel (0.04-0.06 mm), elution
  10. additionbeing carried out under a pressure of 0.5 bar (50 kPa) with a mixture of cyclohexane and ethyl acetate (30/70 by volume) and 50 cc fractions
  11. custombeing collected
  12. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C.

Sources & evidence

ORD record
ord-4213695eaee44126848c4d8b9135311e
Source dataset
uspto-grants-1985_11
Patent number
US04554350

Reaction notes

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