Cycloleucine → 1-[(N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl)amino]cyclopentanecarboxylic acid

HRID 254030

反応式

HRID 254030 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:38]=[CH:37][C:27]([O:28][CH2:29][C:30](NCC(O)=O)=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.C[N:40]1CC[O:43][CH2:42][CH2:41]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:68][C:69]1([C:74]([OH:76])=[O:75])[CH2:73][CH2:72][CH2:71][CH2:70]1.[BH4-].[Na+].C([O-])(=O)C.[NH4+]>CN(C=O)C.CO>[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:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([NH:40][CH2:41][C:42]([NH:68][C:69]3([C:74]([OH:76])=[O:75])[CH2:73][CH2:72][CH2:71][CH2:70]3)=[O:43])=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1

参加物

9

反応物 6

HCID 2901CycloleucineHCID 79724-MethylmorpholineHCID 517165Ammonium AcetateHCID 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}glycine

生成物 1

HCID 668429941-[(N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl)amino]cyclopentanecarboxylic acid収率 49.2%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
30 °C

実験手順

N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.015 g, 0.028 mmol), NMM (0.012 ml, 0.109 mmol) and TBTU (0.011 g, 0.034 mmol) were dissolved in DMF (2 ml) at 30° C. After 30 min 1-amino-1-cyclopentanecarboxylic acid (0.004 g, 0.030 mmol, 97%) was added and the mixture was stirred at 30° C. for 1 h. The reaction was quenched with water (0.2 ml) and the mixture was diluted with MeOH (2 ml). NaBH4 (0.015 g, 0.397 mmol) was added and the mixture was stirred for 10 min. 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 0.1M ammonium acetate buffer as eluent. After freeze-drying, the title compound (0.009 g, 49% yield) was obtained as a white solid. M/z: 654.0. 1H NR (DMSO, 400 M/z): δ 1.56-1.66 (m, 4H), 1.78-1.87 (m, 2H), 1.97-2.07 (m, 2H), 2.84-2.94 (m, 2H), 3.74 (d, 2H), 4.24-4.29 (m, 1H), 4.51 (s, 2H), 4.68-4.76 (m, 1H), 5.02-5.07 (m, 1H), 6.92-7.00 (m, 2H), 7.05-7.26 (m, 6H), 7.29-7.39 (m, 4H), 8.09-8.15 (m, 2H).

後処理

  1. customThe reaction was quenched with water (0.2 ml)
  2. additionthe mixture was diluted with MeOH (2 ml)
  3. stirringthe mixture was stirred for 10 min
  4. customwas removed under reduced pressure
  5. customThe remaining solution was purified by preparative HPLC
  6. customAfter freeze-drying

出典と根拠

ORDレコード
ord-55860c20686641c6bb0cbe16ddd4c970
出典データセット
uspto-grants-2011_01
特許番号
US07871998B2

関連ノート

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