Water → N-({4-[(2R,3R)-3-{[(2R)-2-(4-fluorophenyl)-2-hydroxyethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-3-cyclohexyl-D-alanine

HRID 1176067ノート

反応式

HRID 1176067 の反応式
[Si]([O:8][C@H:9]([C:57]1[CH:62]=[CH:61][C:60]([F:63])=[CH:59][CH:58]=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:56]=[CH:55][C:34]([O:35][CH2:36][C:37]([NH:39][CH2:40][C:41]([NH:43][C@@H:44]([C:52]([OH:54])=[O:53])[CH2:45][CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)=[O:42])=[O:38])=[CH:33][CH:32]=1)(C(C)(C)C)(C)C.O.[Li+].[Cl-].C1(C)C=CC=CC=1>C(O)(=O)C>[F:63][C:60]1[CH:61]=[CH:62][C:57]([C@@H:9]([OH:8])[CH2:10][S:11][C@H:12]2[C:15](=[O:16])[N:14]([C:17]3[CH:18]=[CH:19][C:20]([C:23]#[C:24][CH2:25][NH:26][S:27]([CH3:30])(=[O:28])=[O:29])=[CH:21][CH:22]=3)[C@@H:13]2[C:31]2[CH:32]=[CH:33][C:34]([O:35][CH2:36][C:37]([NH:39][CH2:40][C:41]([NH:43][C@@H:44]([C:52]([OH:54])=[O:53])[CH2:45][CH:46]3[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51]3)=[O:42])=[O:38])=[CH:55][CH:56]=2)=[CH:58][CH:59]=1

参加物

6

反応物 4

HCID 962WaterHCID 1140TolueneHCID 433294Lithium ChlorideHCID 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

生成物 1

HCID 68777557N-({4-[(2R,3R)-3-{[(2R)-2-(4-fluorophenyl)-2-hydroxyethyl]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 176Acetic Acid溶媒2 回

実験手順

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 (16.7 mg, 0.018 mmol) (Method 1) was dissolved in acetic acid (1 ml). Water (0.100 ml) and LiCl (50 mg, 1.18 mmol) were added and the reaction mixture was stirred overnight. The acetic acid was co-evaporated with toluene. The residue was purified with preparative HPLC on a C8 column, UV 235/285 nm. A gradient from 20 to 60% MeCN in 0.1M NH4OAc buffer was used as eluent. The pure fractions were collected and some of MeCN was removed under reduced pressure. The residue was lyophilised to give the title compound. H-NMR (500 MHz, DMSO-d6): 0.73-0.92 (m, 2H), 1.05-1.19 (m, 3H), 1.30 (b, 1H), 1.40-1.70 (m, 7H), 2.93 (d, 2H), 2.97 (s, 3H), 3.76 (d, 2H), 4.00 (s, 2H), 4.14 (bs, 1H), 4.31 (d, 1H), 4.52 (s, 2H), 4.71 (t, 1H), 5.10 (d, 1H), 5.74 (bs, 1H), 6.99 (d, 2H), 7.08-7.13 (m, 2H), 7.20 (d, 2H), 7.32-7.41 (m, 6H), 7.60 (b, 1H), 7.94 (b, 1H), 8.26 (t, 1H). M/z: 809 (M+1) and 807 (M−1).

後処理

  1. customThe residue was purified with preparative HPLC on a C8 column, UV 235/285 nm
  2. customThe pure fractions were collected
  3. customsome of MeCN was removed under reduced pressure

出典と根拠

ORDレコード
ord-356d635a420e4d69a223ff0fd4aa24b8
出典データセット
uspto-grants-2010_11
特許番号
US07842684B2

反応ノート

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