4-Methylmorpholine → N-({4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy)-2-(4-fluorophenyl)ethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-3-cyclohexyl-D-alanine

HRID 1176073ノート

反応式

HRID 1176073 の反応式
[Si:1]([O:8][C@H:9]([C:42]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=1)[CH2:10][S:11][C@H:12]1[C:15](=[O:16])[N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[C:24][CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[CH:19][CH:18]=2)[C@@H:13]1[C:31]1[CH:41]=[CH:40][C:34]([O:35][CH2:36][C:37](O)=[O:38])=[CH:33][CH:32]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:78][CH2:79][C:80]([NH:82][C@@H:83]([C:91]([OH:93])=[O:92])[CH2:84][CH:85]1[CH2:90][CH2:89][CH2:88][CH2:87][CH2:86]1)=[O:81]>CN(C=O)C>[Si:1]([O:8][C@H:9]([C:42]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=1)[CH2:10][S:11][C@H:12]1[C:15](=[O:16])[N:14]([C:17]2[CH:18]=[CH:19][C:20]([C:23]#[C:24][CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[CH:21][CH:22]=2)[C@@H:13]1[C:31]1[CH:32]=[CH:33][C:34]([O:35][CH2:36][C:37]([NH:78][CH2:79][C:80]([NH:82][C@@H:83]([C:91]([OH:93])=[O:92])[CH2:84][CH:85]2[CH2:90][CH2:89][CH2:88][CH2:87][CH2:86]2)=[O:81])=[O:38])=[CH:40][CH:41]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66842930Glycyl-3-cyclohexyl-D-alanineHCID 68774413{4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid

生成物 1

HCID 86628616N-({4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy)-2-(4-fluorophenyl)ethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-3-cyclohexyl-D-alanine

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
30 °C

実験手順

{4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid (Method 8) (25.1 mg, 0.040 mmol) was dissolved in DMF (1 ml, dry). N-methylmorpholine (13 μl, 121 mmol) was added and the reaction mixture was stirred at 30° C. for five minutes. TBTU (20.1 mg, 0.063 mmol) was added and the reaction mixture was stirred at 30° C. for 1 hour. Glycyl-3-cyclohexyl-D-alanine (12.5 mg, 0.055 mmol) was added and the reaction mixture was stirred for 2 hours. The reaction mixture was purified with preparative HPLC on a C8 column. A gradient from 10 to 100% MeCN in 0.1M NH4OAc buffer was used as eluent. Most of the MeCN was removed under reduced pressure. The residue was diluted with water and lyophilised to give the title compound, M/z: 921 (M−1).

後処理

  1. stirringthe reaction mixture was stirred at 30° C. for 1 hour
  2. stirringthe reaction mixture was stirred for 2 hours
  3. customThe reaction mixture was purified with preparative HPLC on a C8 column
  4. customMost of the MeCN was removed under reduced pressure
  5. additionThe residue was diluted with water

出典と根拠

ORDレコード
ord-685892e3f8d746fcbc9fcaa5d7dc0f9a
出典データセット
uspto-grants-2010_11
特許番号
US07842684B2

反応ノート

読み込み中…