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4-Methylmorpholine → N-({4-[(2R,3R)-3-{[2-(1,3-benzodioxol-5-yl)-2-hydroxyethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-b,b-dimethyl-D-phenylalanine

HRID 603902
ノート
印刷プレビュー

反応式

HRID 603902 の反応式
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([OH:40])[CH2:11][S:12][C@H:13]3[C:16](=[O:17])[N:15]([C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=4)[C@@H:14]3[C:25]3[CH:39]=[CH:38][C:28]([O:29]CC(NCC(O)=O)=O)=[CH:27][CH:26]=3)=[CH:9][C:4]=2[O:3][CH2:2]1.C[N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.CN(C([O:55]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.FC(F)(F)C(O)=O.[CH3:77][C:78]([CH3:90])([C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1)[C@H:79]([C:81]([OH:83])=[O:82])[NH2:80]>CN(C=O)C>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([OH:40])[CH2:11][S:12][C@H:13]3[C:16](=[O:17])[N:15]([C:18]4[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=4)[C@@H:14]3[C:25]3[CH:39]=[CH:38][C:28]([O:29][CH2:44][C:43]([NH:42][CH2:47][C:46]([NH:80][C@@H:79]([C:81]([OH:83])=[O:82])[C:78]([CH3:90])([CH3:77])[C:84]4[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=4)=[O:45])=[O:55])=[CH:27][CH:26]=3)=[CH:9][C:4]=2[O:3][CH2:2]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66842897beta,beta-dimethyl-D-phenylalanine trifluoroacetateHCID 67271334N-({4-[(2R,3R)-3-{[2-(1,3-benzodioxol-5-yl)-2-hydroxyethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycine

生成物 1

HCID 67271104
N-({4-[(2R,3R)-3-{[2-(1,3-benzodioxol-5-yl)-2-hydroxyethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-b,b-dimethyl-D-phenylalanine

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
30 °C

実験手順

To a stirred solution of N-({4-[(2R,3R)-3-{[2-(1,3-benzodioxol-5-yl)-2-hydroxyethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycine (15.6 mg, 0.027 mmol) in DMF (2 ml) was added N-methylmorpholine (15 μl, 0.091 mmol). TBTU (12.2 mg, 0.038 mmol) was added and the reaction mixture was stirred at 30° C. for 1 hour. β,β-dimethyl-D-phenylalanine trifluoroacetate (10.2 mg, 0.033 mmol) was added and the mixture was stirred at ambient temperature overnight. The solution was purified with 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 organic phase was passed through a phase separator and concentrated under reduced pressure. The residue was dissolved in MeCN and water. After lyophilisation, the title compound was obtained. H-NMR (400 MHz, DMSO-d6): 1.28 (d, 6H), 2.74-2.92 (m, 2H), 3.58-3.82 (m, 2H) 4.30-4.21 (m, 1H), 4.46 (s, 2H), 4.53-4.65 (m, 2H) 5.00 (b, 0.5H), 5.03 (b, 0.5H), 5.53 (b, 1H), 5.90-5.94 (m, 2H), 6.70-6.79 (m, 2H), 6.82 (s, 1H), 6.90-6.98 (m, 2H), 7.07-7.15 (m, 3H), 7.18-7.26 (m, 4H), 7.27-7.37 (m, 4H), 7.78 (b, 1H), 8.19 (t, 1H). M/z: 742.68 (M−1).

後処理

  1. stirringthe mixture was stirred at ambient temperature overnight
  2. customThe solution was purified with preparative HPLC on a C8 column, UV 240/260 nm
  3. customThe pure fractions were collected
  4. customthe MeCN was removed under reduced pressure
  5. extractionextracted with DCM
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in MeCN

出典と根拠

ORDレコード
ord-d401a8d447334797a4864bfa19e9ed8e
出典データセット
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07906502B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート