Methanol → HCID 22896667, compound

HRID 1280103Notes

Reaction equation

HRID 1280103 reaction equation
[N:1]([C:4]1[CH:5]=[C:6]([CH2:11][C@H:12]([NH:16][C:17]([C:19]2[CH:38]=[CH:37][C:22]3[N:23]([CH:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)[C:24]([C:26]4[CH:30]=[CH:29][O:28][CH:27]=4)=[N:25][C:21]=3[CH:20]=2)=[O:18])[C:13]([OH:15])=[O:14])[CH:7]=[CH:8][C:9]=1[OH:10])=[N+:2]=[N-:3].Br[CH2:40][C:41]([O:43]C)=[O:42].C([O-])([O-])=O.[Cs+].[Cs+].CO>CC(C)=O.C1COCC1>[N:1]([C:4]1[CH:5]=[C:6]([CH2:11][C@H:12]([NH:16][C:17]([C:19]2[CH:38]=[CH:37][C:22]3[N:23]([CH:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)[C:24]([C:26]4[CH:30]=[CH:29][O:28][CH:27]=4)=[N:25][C:21]=3[CH:20]=2)=[O:18])[C:13]([OH:15])=[O:14])[CH:7]=[CH:8][C:9]=1[O:10][CH2:40][C:41]([OH:43])=[O:42])=[N+:2]=[N-:3]

Participants

7

Reactant 4

HCID 887MethanolHCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 3003568(2S)-3-(3-azido-4-hydroxy-phenyl)-2-[[1-cyclohexyl-2-(3-furyl)benzimidazole-5-carbonyl]amino]propanoic acid

Product 1

HCID 22896667HCID 22896667, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(S)-3-(3-Azido-4-hydroxy-phenyl)-2-{[1-(1-cyclohexyl-2-furan-3-yl-1H-benzoimidazol-5-yl)-methanoyl]-amino}-propionic acid (Example 146, 0.230 g, 0.44 mmol) and methyl bromoacetate (0.136 g, 0.89 mmol) were stirred in acetone (4 mL) in the presence of Cs2CO3 (0.058 g, 0.18 mmol) for 20 h at room temperature. The reaction mixture was concentrated to dryness and dissolved in water, acidify to pH 4 and extracted with EtOAc (3×). The combined organic layers were dried over anhydrous MgSO4 and concentrated to give a brown oil. This oil was stirred in THF:MeOH (6 mL, 2:1 ratio) in the presence of LiOH monohydrate (0.18 mmol) for 3 h at room temperature. The reaction mixture was concentrated to remove most of the THF and MeOH, acidified with AcOH and purified by reversed phase C18 preparative HPLC to obtain the title compound of example 147.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. dissolutiondissolved in water
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  5. concentrationconcentrated
  6. customto give a brown oil
  7. concentrationThe reaction mixture was concentrated
  8. customto remove most of the THF and MeOH
  9. custompurified by reversed phase C18 preparative HPLC

Sources & evidence

ORD record
ord-0e1e8472047847d581c271b060e05c48
Source dataset
uspto-grants-2002_09
Patent number
US06448281B1

Reaction notes

Loading…