HCID 66842673, compound → HCID 66843232, compound

HRID 254020Notes

Reaction equation

HRID 254020 reaction equation
[CH:1]1([C@@H:7]([NH:11][C:12](=[O:48])[CH2:13][NH:14][C:15](=[O:47])[CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C@@H:24]3[C@@H:27]([S:28][CH2:29][C:30]([C:32]4[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=4)=[O:31])[C:26](=[O:39])[N:25]3[C:40]3[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=3)=[CH:20][CH:19]=2)[C:8]([OH:10])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>CO.C(O)(=O)C>[CH:1]1([C@@H:7]([NH:11][C:12](=[O:48])[CH2:13][NH:14][C:15](=[O:47])[CH2:16][O:17][C:18]2[CH:19]=[CH:20][C:21]([C@@H:24]3[C@@H:27]([S:28][CH2:29][CH:30]([C:32]4[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=4)[OH:31])[C:26](=[O:39])[N:25]3[C:40]3[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=3)=[CH:22][CH:23]=2)[C:8]([OH:10])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 1

HCID 66842673HCID 66842673, compound

Product 1

HCID 66843232HCID 66843232, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

(2R)-cyclohexyl[(N-([4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio)-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl)amino]acetic acid (0.0085 g, 0.013 mmol) was dissolved in methanol (2 ml). NABH4 (0.006 g, 0.159 mmol) was added and when the reaction was complete according to LC-MS a few drops of acetic acid was added. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC on a Kromasil C8-column using a stepwise gradient of 35%, 40% then 50% MeCN in 0.1M ammonium acetate buffer as eluent. After freeze-drying, 0.007 g (82%) of the title product was obtained. NMR (500 MHz, CD3COOD) 1.05-1.33 (m, 5H), 1.60-1.87 (m, 6H), 2.91-3.07 (m, 2H), 3.94-4.06 (m, 3H), 4.32 (d, 1H), 4.60 (s, 2H), 4.79-4.86 (m, 1H), 4.90 (d, 0.5H), 4.92 (d, 0.5H), 6.96-7.03 (m, 4H), 7.03-7.08 (brd, 2H), 7.25-7.31 (m, 2H), 7.31-7.38 (m, 4H)

Workup

  1. additionNABH4 (0.006 g, 0.159 mmol) was added
  2. additionwas added
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by preparative HPLC on a Kromasil C8-column
  5. customAfter freeze-drying

Sources & evidence

ORD record
ord-794f273d10f448908e4bd9cba9212238
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

Loading…