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

HRID 254066
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HRID 254066 반응식
[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(NCC(O)=O)=O)=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.[CH3:39][N:40]1CC[O:43][CH2:42][CH2:41]1.CN(C([O:53]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.FC(F)(F)C(O)=O.[CH3:75][C:76]([CH3:88])([C:82]1[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=1)[C@H:77]([C:79]([OH:81])=[O:80])[NH2:78]>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:39]([NH:40][CH2:41][C:42]([NH:78][C@@H:77]([C:79]([OH:81])=[O:80])[C:76]([CH3:88])([CH3:75])[C:82]3[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=3)=[O:43])=[O:53])=[CH:37][CH:38]=2)=[CH:6][CH:7]=1
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참가 물질

6

반응물 4

HCID 79724-MethylmorpholineHCID 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}glycineHCID 66842897beta,beta-dimethyl-D-phenylalanine trifluoroacetate

생성물 1

HCID 16092141
N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2 hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-b,b-dimethyl-D-phenylalanine

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
30 °C

실험 절차

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 (25.2 mg, 0.047 mmol) in DMF (2 ml) was added N-methylmorpholine (30 μl, 0.027 mmol). TBTU (18.0 mg, 0.056 mmol) was added and the mixture was stirred at 30° C. for 1 hour. β, β-dimethyl-D-phenylalanine trifluoroacetate was added and the mixture was stirred at 30° C. for 1.25 hours. The formation of the ketone of the title compound was confirmed. M/z: 716.07 (M+1) and 714.05 (M−1). Water (0.5 ml) was added. Methanol (2 ml) and sodium borohydride (18.2 mg, 0.48 mmol) were added the mixture was stirred for 25 minutes. Ammonium acetate (30 mg) was added and the methanol was removed under reduced pressure. The remaining DMF-solution was purified with preparative HPLC. A gradient from 20 to 48% MeCN in 0.1M NH4OAc buffer was used as eluent. The MeCN was removed under reduced pressure and the remaining water solution was acidified to pH 1 with HCl (1M) and extracted with DCM. The organic phase was concentrated under reduced pressure and the residue was dissolved in MeCN and water. After lyophilisation, the title compound was obtained as a white solid (20.5 mg, 62%). H-NMR (400 MHz, DMSO-d6): 1.27-1.32 (m, 6H), 2.75-3.05 (m, 2H), 3.55-3.67 (m, 1H), 3.79 (dd, 1H), 4.25-4.30 (m, 0.5H), 4.40 (s, 0.5H), 4.45-4.53 (m, 3H), 4.68-4.78 (m, 1H), 4.99 (d, 0.5H), 4.05 (d, 0.5H), 6.88-6.98 (m, 2H), 7.05-7.17 (m, 5H), 7.20-7.40 (m, 10H) 7.45-7.75 (m, 1H) 8.22 (t, 1H). M/z: 718.09 (M+1) and 716.07 (M−1).

후처리

  1. stirringthe mixture was stirred at 30° C. for 1.25 hours

출처 및 근거

ORD 기록
ord-41e7ffd936514813b72119552deb907e
출처 데이터셋
uspto-grants-2011_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07871998B2

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