4-Methylmorpholine → HCID 66843128, compound

HRID 254048Notes

Reaction equation

HRID 254048 reaction equation
CN(C(ON1N=NC2C=CC=CC1=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](O)=[O:57])=[O:53])=[CH:48][CH:47]=2)=[CH:26][CH:25]=1.CN1CCOCC1.FC(F)(F)C(O)=O.[C:75]1([CH:81]([C:87]2[CH:92]=[CH:91][CH:90]=[CH:89][CH:88]=2)[C@H:82]([C:84]([OH:86])=[O:85])[NH2:83])[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1.[BH4-].[Na+]>C(Cl)Cl.CO.O>[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][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:60]=[CH:59][C:49]([O:50][CH2:51][C:52]([NH:54][CH2:55][C:56]([NH:83][C@@H:82]([C:84]([OH:86])=[O:85])[CH:81]([C:87]3[CH:88]=[CH:89][CH:90]=[CH:91][CH:92]=3)[C:75]3[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=3)=[O:57])=[O:53])=[CH:48][CH:47]=2)=[CH:26][CH:25]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 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}glycineHCID 66842872HCID 66842872, compound

Product 1

HCID 66843128HCID 66843128, compoundYield 59.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

TBTU (0.018 g, 0.056 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 (0.025 g, 0.046 mmol) and N-methylmorpholine (0.023 g, 0.231 mmol) in CH2Cl2 (5 ml) at 30° C. After 1.5 h, β-phenyl-D-phenylalanine trifluoro acetic acid salt (0.033 g, 0.092 mmol) was added. The mixture was stirred for 5 minutes. Water (1 ml) was added and the mixture was concentrated. MeOH (3 ml) and NaBH4 (0.017 g, 0.462 mmol) were added. After 5 minutes, the reaction was quenched by the addition of 0.1M NH4OAc buffer (1 ml) followed by concentration of the mixture. Purification by preparative HPLC using an eluent of 0-45% CH3CN in 0.1M NH4OAc buffer and lyophilisation gave the title compound (0.021 g, 59%) as a colourless solid. M/z: 764.1 (M−1). 1H NMR [(CD3)2SO), 400 MHz] δ 2.82-2.95 (m, 2H), 3.42-3.49 (m, 1H), 3.66-3.74 (m, 1H), 4.25-4.33 (m, 2H), 4.42 (d, 1H), 4.47 (d, 1H), 4.69-4.76 (m, 1H), 5.03-5.12 (m, 2H), 6.94-7.38 (m, 2H), 8.10-8.14 (m, 1H), 8.18-8.24 (m, 1H).

Workup

  1. concentrationthe mixture was concentrated
  2. waitAfter 5 minutes
  3. customthe reaction was quenched by the addition of 0.1M NH4OAc buffer (1 ml)
  4. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-6f0166ce458d49f09e6a15396b3a309e
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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