4-Methylmorpholine → HCID 66842997, compound

HRID 254062

Reaction equation

HRID 254062 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34](O)=[O:35])=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:68]([O:75][CH2:76][C@@H:77]([C:79]([OH:81])=[O:80])[NH2:78])[C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][CH:15]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[OH:16])[C@H:9]2[C:24]2[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34]([NH:78][C@H:77]([C:79]([OH:81])=[O:80])[CH2:76][O:75][CH2:68][C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=3)=[O:35])=[O:31])=[CH:37][CH:38]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 78457O-benzyl-L-serineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66842760N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio)-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine

Product 1

HCID 66842997HCID 66842997, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

To a stirred solution of N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine, (20.3 mg, 0.038 mmol) in DMF (2 ml) was added N-methylmorpholine (15 μl, 0.14 mmol). TBTU (14.8 mg, 0.046 mmol) was added the mixture was stirred at 30° C. for 1.5 hours. O-benzyl-L-serine (8.8 mg, 0.045 mmol) was added and the mixture was stirred overnight. The formation of the ketone of the title compound was confirmed. M/z: 718.04 (M+1) and 716.02 (M−1). Methanol (3 ml) and sodium borohydride (10.3 mg, 0.27 mmol) were added and the mixture was stirred for 1.5 hours. Ammonium acetate (20 mg) was added and the methanol was removed under reduced pressure. The remaining DMF-solution was purified by preparative HPLC on a C8 column, UV 240/260 nm. A gradient from 20 to 45% MeCN in 0.1M NH4OAc buffer was used as eluent. The pure fractions were collected and the MeCN was removed under reduced pressure. The remaining water solution was acidified to pH 1 with HCl (1M) and extracted with DCM. The combined organic phases were concentrated and the residue was dissolved in MeCN and water. After lyophilisation, the title compound was obtained as a white solid (2.3 mg, 8.5%).

Workup

  1. stirringthe mixture was stirred overnight

Sources & evidence

ORD record
ord-76b03bd32d2542ffadc6da974bc09f0f
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Linked notes

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