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-D-lysine

HRID 1176070Notes

Reaction equation

HRID 1176070 reaction equation
[Si]([O:8][C@H:9]([C:62]1[CH:67]=[CH:66][C:65]([F:68])=[CH:64][CH:63]=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:61]=[CH:60][C:34]([O:35][CH2:36][C:37]([NH:39][CH2:40][C:41]([NH:43][C@@H:44]([C:57]([OH:59])=[O:58])[CH2:45][CH2:46][CH2:47][CH2:48][NH:49]C(OC(C)(C)C)=O)=[O:42])=[O:38])=[CH:33][CH:32]=1)(C(C)(C)C)(C)C.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[Ce+4].[N+]([O-])(O)=O.O>CC#N>[F:68][C:65]1[CH:66]=[CH:67][C:62]([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:57]([OH:59])=[O:58])[CH2:45][CH2:46][CH2:47][CH2:48][NH2:49])=[O:42])=[O:38])=[CH:60][CH:61]=2)=[CH:63][CH:64]=1

Participants

5

Reactant 3

HCID 962WaterHCID 86628618N-({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-N6-(tert-butoxycarbonyl)-D-lysineHCID 86628619Cerium(4+) tetranitrate nitric acid

Product 1

HCID 68780074N-({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-D-lysine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

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-N6-(tert-butoxycarbonyl)-D-lysine (Method 2) (21.9, 0.022 mmol) was dissolved in MeCN (1.5 ml). Cerium(4+) tetranitrate-nitric acid (1:2) diammoniate (25.1 mg, 0.046 mmol) and water (50 μl) were added. The reaction mixture was heated at 45° C. for 6 h and 30 minutes and it was allowed to stand at room temperature over the weekend. The solution was purified with preparative HPLC on a C8 column, UV 235/285 nm. A gradient from 10 to 90% MeCN in 0.1M NH4OAc buffer was used as eluent. Most of the MeCN was removed under reduced pressure and the residue was lyophilised to give the title compound as a yellow solid. H-NMR (500 MHz, DMSO-d6): 1.13-1.66 (m, 6H), 2.64-2.71 (m, 2H), 2.90-2.96 (m, 2H), 2.97 (s, 3H), 3.62-3.80 (m, 3H), 4.00 (s, 2H), 4.34 (d, 1H), 4.53 (s, 2H), 4.72 (t, 1H), 5.09 (d, 1H), 6.99 (d, 2H), 7.07-7.13 (m, 2H), 7.20 (d, 2H), 7.32-7.40 (m, 6H), 7.46 (b, 1H), 8.42 (t, 1H). M/z: 782.58 (M−1) and 784.42 (M+1).

Workup

  1. customto stand at room temperature over the weekend
  2. customThe solution was purified with preparative HPLC on a C8 column, UV 235/285 nm
  3. customMost of the MeCN was removed under reduced pressure

Sources & evidence

ORD record
ord-5a992faa5c254edfa1f09ca837276a22
Source dataset
uspto-grants-2010_11
Patent number
US07842684B2

Reaction notes

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