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Trifluoroacetic acid → N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethy]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}-L-alanyl-D-valine

HRID 254029
ノート
印刷プレビュー

反応式

HRID 254029 の反応式
[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:39]=[CH:38][C:27]([O:28][CH2:29][C:30]([NH:32][C@H:33]([C:35]([OH:37])=O)[CH3:34])=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.Cl.C([O:45][C:46](=[O:52])[C@@H:47]([CH:49]([CH3:51])[CH3:50])[NH2:48])(C)(C)C.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(O)(C(F)(F)F)=O>C(Cl)Cl.C1(C)C=CC=CC=1>[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:30]([NH:32][C@H:33]([C:35]([NH:48][C@@H:47]([C:46]([OH:52])=[O:45])[CH:49]([CH3:51])[CH3:50])=[O:37])[CH3:34])=[O:31])=[CH:38][CH:39]=2)=[CH:6][CH:7]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 45108216H-D-Val-OtBu hydrochlorideHCID 66842883N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}-L-alanine

生成物 1

HCID 66842877
N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethy]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}-L-alanyl-D-valine
収率 79.1%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒

実験手順

A solution of N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-([2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}-L-alanine (0.015 g, 0.027 mmol), D-valine tert-butyl ester hydrochloride (0.008 g, 0.038 mmol) and N-methylmorpholine (0.030 ml, 0.272 mmol) in DCM (4 ml) was stirred for 5 min. TBTU (0.013 g, 0.041 mmol) was added. After 3 h, the conversion to the ester (M/z: 710.2) was completed and TFA (3 ml) was added. After 4 h, the mixture was diluted with toluene (2 ml) and the solvent was removed under reduced pressure. The residue was dissolved in MeOH (4 ml) and NaBH4 was added in small portions to the solution (a total of 0.065 g, 1.72 mmol) until the reduction was complete. 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 a 0.1M ammonium acetate buffer as eluent. After freeze-drying, 0.014 g (77% yield) of the title compound was obtained as a white solid. M/z: 656.1. 1H NMR (DMSO, 400 MHz): δ 0.75-0.83 (m, 6H), 1.22 (d, 3H), 1.95-2.07 (m, 1H), 3.83-3.96 (m, 2H), 3-98-4.06 (m, 1H), 4-24-4.31 (m, 1H), 4.40-4.54 (m, 3H), 4.67-4.76 (m, 1H), 5.01-5.07 (m, 1H), 6.91-7.98 (m, 2H), 7.05-7.17 (m, 4H), 7.19-7.25 (m, 2H), 7.29-7.39 (m, 4H), 7.84-7.95 (m, 1H). 8.07 (d, 1H),

後処理

  1. waitAfter 4 h
  2. customthe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in MeOH (4 ml)
  4. additionNaBH4 was added in small portions to the solution (a total of 0.065 g, 1.72 mmol) until the reduction
  5. additionAmmonium acetate buffer (0.1M, 3 ml) was added and most of the methanol
  6. customwas removed under reduced pressure
  7. customThe remaining solution was purified by preparative HPLC
  8. customAfter freeze-drying

出典と根拠

ORDレコード
ord-d1d1d9e048a64a2c9b8d87a6ba1383f9
出典データセット
uspto-grants-2011_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07871998B2

反応ノート

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