Methanol → HCID 22896667, compound

HRID 2117027Notes

Reaction equation

HRID 2117027 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-1 H-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-a887814d1771493dacee15730663d32d
Source dataset
uspto-grants-2008_10
Patent number
US07439258B2

Reaction notes

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