Methanesulfonyl chloride → tert-butyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-(oxolan-3-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1421805Notes

Reaction equation

HRID 1421805 reaction equation
Cl.[CH3:2][O:3]/[N:4]=[C:5](/[C:9]1[N:10]=[C:11]([NH:14][C:15]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[S:12][CH:13]=1)\[C:6]([OH:8])=O.CS(Cl)(=O)=O.C(N(C(C)C)CC)(C)C.[NH2:48][C@@H:49]1[C:68](=[O:69])[N:51]2[C:52]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])=[C:53]([CH:56]3[CH2:60][CH2:59][O:58][CH2:57]3)[CH2:54][S:55][C@H:50]12>CN(C=O)C.N1C=CC=CC=1>[CH3:2][O:3]/[N:4]=[C:5](/[C:9]1[N:10]=[C:11]([NH:14][C:15]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[S:12][CH:13]=1)\[C:6]([NH:48][C@@H:49]1[C:68](=[O:69])[N:51]2[C:52]([C:61]([O:63][C:64]([CH3:65])([CH3:66])[CH3:67])=[O:62])=[C:53]([CH:56]3[CH2:60][CH2:59][O:58][CH2:57]3)[CH2:54][S:55][C@H:50]12)=[O:8]

Participants

7

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 95660662-(Tritylamino)-alpha-(methoxyimino)-4-thiazoleacetic acid, predominantly syn hydrochlorideHCID 54127982t-Butyl (6R,7R)-7-Amino-3-[(RS)-tetrahydrofuran-3-yl]ceph-3-em-4-carboxylate

Product 1

HCID 141582263tert-butyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-(oxolan-3-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent2×

Procedure

2-(Z)-Methoxyimino-2-(2-tritylaminothiazol-4-yl)acetic acid hydrochloride (0.751 g) in DMF (5 ml) was treated with methanesulphonyl chloride (0.179 g, 0.121 ml) and diisopropylethylamine (0.404 g, 0.544 ml) as described in Example 1(g). This was then treated with t-butyl (6R,7R)-7-amino-3-[(RS)-tetrahydrofuran-3-yl]ceph-3-em-4-carboxylate (0.464 g) and pyridine (0.112 g, 0.114 ml) in DMF (5 ml). Following work up and purification by flash chromatography with 40, 50 and 60% ethyl acetate/hexane, the title compound was obtained as a yellow foam (0.874 g, 82%); νmax (CH2Cl2) 3398, 1783, 1731 (shoulder), 1718 and 1688 cm-1 ; δH (CDCl3) 1.53 (9H, s), 1.69-2.43 (3H, m's), 3.29 and 3.46 with 3.34 and 3.48 (2H, 2ABq's, J 17.7 and 17.7 Hz), 3.63-4.07 (6H, m's and s), 5.03 and 5.06 (1H, 2d's, J 4.8 and 4.8 Hz), 5.84-5.90 (1H, m), 6.73 and 6.74 (1H, 2s), 6.76 and 6.90 (1H, 2d's, J 8.7 and 8.7 Hz exchangeable with D2O), 7.02 (1H, br. s, exchangeable with D2O) and 7.31 (15H, s). [Mass spectrum: +ve ion (3NOBA, Na+) MNa+ (774)].

Workup

  1. custompurification by flash chromatography with 40, 50 and 60% ethyl acetate/hexane

Sources & evidence

ORD record
ord-50f5a11eb9c94f0495839897f7a0474d
Source dataset
uspto-grants-2000_06
Patent number
US06077952

Reaction notes

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