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

HRID 376572Notes

Reaction equation

HRID 376572 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 538410274-Methoxybenzyl (6R,7R)-7-Amino-3-((R)-tetrahydrofuran-2-yl)ceph-3-em-4-carboxylate

Product 1

HCID 88258980(4-methoxyphenyl)methyl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2R)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-30 °C

Procedure

Methanesulphonyl chloride (198μl, 2.56mmol) was added to 2-(2-aminothiazol-4-yl)-2-(Z)-methoxyiminoacetic acid (515mg, 2.56mmol) and N,N-diisopropylethylamine (447μl, 2.57mmol) in DMF (8ml) at -30° C. After stirring at -30±10° C. for 30 min., a solution of 4-methoxybenzyl (6R, 7R) -7-amino-3-[(R)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (915mg, 2.35mmol) in DMF (5ml) was added, followed by pyridine (207μl, 2.56mmol). The reaction mixture was transferred to an ice-bath and stirring continued for a further 1.5h. 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 triturated several times with diethyl ether to yield the title compound as an off-white solid (1.06g, 79%); vmax (CH2Cl2) 3390, 1783, 1730, 1687, 1606, 1516cm-1 ; δH (CDCl3, 250MHz) 1.55-1.70 (1H, m), 1.86-1.98 (2H, m), 2.0-2.14 (1H, m), 3.40 and 3.59 (2H, ABq, J 17.8Hz), 3.78-3.93 (2H, m), 3.91 (3H, s), 4.12 (3H, s), 5.04 (1H, d, J 4.7Hz), 5.15 (1H, dd, J 7.7, 7.7Hz), 5.21 (2H, s), 5.87 (1H, dd, J 8.7, 4.7Hz), 6.55 (2H, br. s, exch.), 6.90 (2H, d, J 8.6Hz), 7.05 (1H, s), 7.36 (2H, d, J 8.6Hz), 7.65 (1H, br. d, J 8.7Hz). [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 1.5h
  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 triturated several times with diethyl ether

Sources & evidence

ORD record
ord-3c110448d4ab4420a087351976a94a32
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

Loading…