Pyridine → (4-methoxyphenyl)methyl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2S)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 612286Notes

Reaction equation

HRID 612286 reaction equation
CS(Cl)(=O)=O.[NH2:6][C:7]1[S:8][CH:9]=[C:10](/[C:12](=[N:16]/[O:17][CH3:18])/[C:13]([OH:15])=O)[N:11]=1.C(N(CC)C(C)C)(C)C.[NH2:28][C@@H:29]1[C:53](=[O:54])[N:31]2[C:32]([C:41]([O:43][CH2:44][C:45]3[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][CH:46]=3)=[O:42])=[C:33]([C@@H:36]3[CH2:40][CH2:39][CH2:38][O:37]3)[CH2:34][S:35][C@H:30]12.N1C=CC=CC=1>CN(C=O)C>[NH2:6][C:7]1[S:8][CH:9]=[C:10](/[C:12](=[N:16]/[O:17][CH3:18])/[C:13]([NH:28][C@@H:29]2[C:53](=[O:54])[N:31]3[C:32]([C:41]([O:43][CH2:44][C:45]4[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][CH:46]=4)=[O:42])=[C:33]([C@@H:36]4[CH2:40][CH2:39][CH2:38][O:37]4)[CH2:34][S:35][C@H:30]23)=[O:15])[N:11]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 5486924(alphaZ)-2-Amino-alpha-(methoxyimino)-4-thiazoleacetic acidHCID 538410264-methoxybenzyl (6R,7R)-7-amino-3-[(S)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate

Product 1

HCID 141582268(4-methoxyphenyl)methyl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2S)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 83.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-30 °C

Procedure

Methanesulphonyl chloride (203 μl, 2.62 mmol) was added to 2-(2-aminothiazol-4-yl)-2-(Z)-methoxyiminoacetic acid (528 mg, 2.63 mmol) and N,N-diisopropylethylamine (458 μl, 2.63 mmol) in DMF (8 ml) at -30° C. After stirring at -30±10° C. for 30 min., a solution of 4-methoxybenzyl (6R,7R)-7-amino-3-[(S)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (930 mg, 2.38 mmol) in DMF (5 ml) was added, followed by pyridine (213 μl, 2.63 mmol). The reaction mixture was transferred to an ice-bath and stirring continued for a further 1 h. After dilution with ethyl acetate, the solution was washed successively with saturated sodium hydrogen carbonate solution, 5% aqueous citric acid, water (x2) and brine, dried and then concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with 50, 70 and 90% ethyl acetate in hexane to give the title compound as a yellow foam (1.138 g, 83%); νmax (CH2Cl2) 3389, 1783, 1732, 1682, 1516 cm-1 ; δH (CDCl3, 250 MHz) 1.53-1.70 (1 H, m), 1.88-2.01 (2 H, m), 2.28-2.41 (1 H, m), 3.33 and 3.62 (2 H, ABq, J 18.7 Hz), 3.79-3.98 (2 H, m), 3.81 (3 H, s), 4.08 (3 H, s), 4.94 (1 H, dd, J 9.0, 6.7 Hz), 5.04 (1 H, d, J 4.8 Hz), 5.18 (2 H, s), 5.88 (2 H, br s, exch.), 5.98 (1 H, dd, J 9.0, 4.8 Hz), 6.90 (2 H, d, J 8.6 Hz), 6.94 (1 H, s), 7.35 (2 H, d, J 8.6 Hz), 7.50 (1 H, br. d, J 9.0 Hz, exch.). [Mass spectrum: +ve ion (thioglycerol) MH+ (574)].

Workup

  1. customThe reaction mixture was transferred to an ice-bath
  2. stirringstirring
  3. waitcontinued for a further 1 h
  4. washAfter dilution with ethyl acetate, the solution was washed successively with saturated sodium hydrogen carbonate solution, 5% aqueous citric acid, water (x2) and brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography on silica gel eluting with 50, 70 and 90% ethyl acetate in hexane

Sources & evidence

ORD record
ord-951a35ffd22144f58ba62a4b5ad7e0df
Source dataset
uspto-grants-1999_12
Patent number
US06001997

Reaction notes

Loading…