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 1176067Notes

Reaction equation

HRID 1176067 reaction equation
[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

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-356d635a420e4d69a223ff0fd4aa24b8
Source dataset
uspto-grants-2010_11
Patent number
US07842684B2

Reaction notes

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