4-Methylmorpholine → N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-N-benzylglycine

HRID 254031Notes

Reaction equation

HRID 254031 reaction equation
CN(C(ON1N=N[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[F:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]2[C:33](=[O:34])[C@H:32]([S:35][CH2:36][C:37]([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)=[O:38])[C@H:31]2[C:46]2[CH:60]=[CH:59][C:49]([O:50][CH2:51][C:52]([NH:54][CH2:55][C:56]([OH:58])=O)=[O:53])=[CH:48][CH:47]=2)=[CH:26][CH:25]=1.[CH3:61][N:62]1CCOCC1.[BH4-].[Na+].[C:70]([O-:73])(=[O:72])[CH3:71].[NH4+]>CN(C=O)C.CO>[F:23][C:24]1[CH:25]=[CH:26][C:27]([N:30]2[C:33](=[O:34])[C@H:32]([S:35][CH2:36][CH:37]([C:39]3[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=3)[OH:38])[C@H:31]2[C:46]2[CH:47]=[CH:48][C:49]([O:50][CH2:51][C:52]([NH:54][CH2:55][C:56]([N:62]([CH2:61][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:71][C:70]([OH:73])=[O:72])=[O:58])=[O:53])=[CH:59][CH:60]=2)=[CH:28][CH:29]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 517165Ammonium AcetateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 4311764Sodium borohydrideHCID 66842760N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio)-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine

Product 1

HCID 66843297N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-N-benzylglycineYield 53%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

TBTU (0.011 g, 0.034 mmol) was added to a solution of N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.015 g, 0.028 mmol) and NMM (0.020 ml, 0.182 mmol) in DMF (2 ml) at 30° C. After 30 min, N-enzylglycine (0.005 g, 0.030 mmol, 98%) was added and the mixture was stirred at 30° C. for 1 h. The reaction was quenched with water (0.2 ml) and the mixture was diluted with MeOH (2 ml). NaBH4 (0.015 g, 0.397 mmol) was added and the mixture was stirred for 10 min. Ammonium acetate buffer (0.1M, 3 ml) was added and most of the methanol was removed under reduced pressure. The remaining solution was purified by preparative HPLC, using a gradient of 20-50% MeCN in 0.1M ammonium acetate buffer as eluent. After freeze-drying, the title compound (0.010 g, 53% yield) was obtained as a white solid. M/z: 690.0. 1H NMR (DMSO, 400 MHz): δ 2.83-2.94 (m, 2H), 3.91 (s, 1H), 3.98-4.09 (m, 3H), 4.25-4.29 (m, 1H), 4.50 (s, 2H), 4.54 (s, 1H), 4.62 (s, 1H), 4.68-4.76 (m, 1H), 5.02-5.07 (m, 1H), 6.92-7.02 (m, 2H), 7.05-7.40 (m, 15H), 8.14-8.21 (m, 1H).

Workup

  1. additionN-enzylglycine (0.005 g, 0.030 mmol, 98%) was added
  2. customThe reaction was quenched with water (0.2 ml)
  3. additionthe mixture was diluted with MeOH (2 ml)
  4. stirringthe mixture was stirred for 10 min
  5. customwas removed under reduced pressure
  6. customThe remaining solution was purified by preparative HPLC
  7. customAfter freeze-drying

Sources & evidence

ORD record
ord-3ed486a7808f404da3c2f38ca3b46d44
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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