4-Methylmorpholine → HCID 66842855, compound

HRID 254047Notes

Reaction equation

HRID 254047 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]([OH:80])[C@@H:69]([OH:79])[C@@H:70]([OH:78])[C@H:71]([OH:77])[C@@H:72]([NH2:76])[C:73]([OH:75])=[O:74]>CS(C)=O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[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][CH:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=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:76][C@@H:72]([C:73]([OH:75])=[O:74])[C@@H:71]([OH:77])[C@H:70]([OH:78])[C@H:69]([OH:79])[CH2:68][OH:80])=[O:35])=[O:31])=[CH:37][CH:38]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 735632-amino-2-deoxygluconic acid,HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2×HCID 66842760N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio)-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine

Product 1

HCID 66842855HCID 66842855, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

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) was dissolved in DMSO (2 ml) at 30° C. N-Methylmorpholine (0.014 g, 0.139 mmol) and TBTU (0.018 g, 0.056 mmol) were added. After 1 h, D-glucosaminic acid (0.018 g, 0.092 mmol) and tetrabutylammoniumbromide (0.001 g, 0.005 mmol) were added. The mixture was stirred for 15 minutes. Additional TBTU (18 mg, 0.056 mmol) was added. After 30 minutes, approximately 30% amide formation had occurred. The reaction was quenched by the addition of 0.1M NH4OAc buffer (2 ml). The intermediate ketone was purified by preparative HPLC using an eluent of 0-50% CH3CN in 0.1M NH4OAc buffer and freeze-dried. MeOH (3 ml) and NABH4 (0.005 g, 0.139 mmol) were added. After 5 minutes, the reaction was quenched by the addition of 0.1M NH4OAc buffer (1 ml). Concentration of the mixture and purification by preparative HPLC using an eluent of 0-50% CH3CN in 0.1M NH4OAc buffer gave the title compound (0.005 g, 16%) as a colourless solid. M/z: 718.0 (M−1). 1H NMR [(CD3)2SO), 400 MHz] δ 2.82-2.94 (m, 2H), 3.34-3.56 (m, 4H), 3.76-3.80 (m, 2H), 3.87-3.90 (m, 1H), 4.07-4.11 (m, 1H), 4.27-4.32 (m, 1H), 4.52 (s, 2H), 4.68-4.76 (m, 1H), 5.02-5.05 (m, 1H), 6.97-7.39 (m, 12H), 7.63-7.70 (m, 1H), 8.28-8.35 (m, 1H).

Workup

  1. waitAfter 30 minutes
  2. customThe reaction was quenched by the addition of 0.1M NH4OAc buffer (2 ml)
  3. customThe intermediate ketone was purified by preparative HPLC
  4. customfreeze-dried
  5. additionMeOH (3 ml) and NABH4 (0.005 g, 0.139 mmol) were added
  6. waitAfter 5 minutes
  7. customthe reaction was quenched by the addition of 0.1M NH4OAc buffer (1 ml)
  8. customConcentration of the mixture and purification by preparative HPLC

Sources & evidence

ORD record
ord-d0667c2ea1ab4322a12293ed180cdb15
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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