Lithium Hydroxide → HCID 178438092, compound

HRID 2401148Notes

Reaction equation

HRID 2401148 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:19][C:18]([O:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([C:27]([O:29]CC)=[O:28])[CH2:23][CH2:22]3)=[N:17][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11](F)=[C:10]([C:15]#[N:16])[CH:9]=1.[C:32](=O)([O-])[O-].[Cs+].[Cs+].[CH3:38][C:39]1([OH:43])[CH2:42][NH:41][CH2:40]1.[Li+].[OH-]>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:19][C:18]([O:20][C@H:21]3[CH2:22][CH2:23][C@H:24]([C:27]([OH:29])=[O:28])[CH2:25][CH2:26]3)=[N:17][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([O:43][C:39]2([CH2:38][CH3:32])[CH2:42][NH:41][CH2:40]2)=[C:10]([C:15]#[N:16])[CH:9]=1

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 10796Cesium carbonateHCID 115427823-Methylazetidin-3-olHCID 178472484HCID 178472484, compound

Product 1

HCID 178438092HCID 178438092, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of ethyl trans-4-{[6-chloro-5-(3-cyano-4-fluorophenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy}cyclohexanecarboxylate (30 mg, 0.075 mmol) in DMSO (400 μL) was added cesium carbonate (48.9 mg, 0.150 mmol) and 3-methylazetidin-3-ol (2.55 mg, 0.150 mmol). The reaction was heated to 90° C. over 4 h. The reaction was cooled, then quenched with citric acid, and extracted with EtOAc. LiOH (100 μL, 0.200 mmol) was added and the reaction was stirred overnight. The reaction was then quenched with citric acid (2 mL, 10% w/v) and extracted with EtOAc (2×5 mL). The organic layers were combined and concentrated in vacuo to give a crude residue, which was purified via reverse phase HPLC to afford the title compound as white powder. LC-MS: calculated for C24H24ClN5O4 481.2, observed m/e: 482.1 (M+H)+ (Rt 0.8/2 min).

Workup

  1. temperatureThe reaction was cooled
  2. customquenched with citric acid
  3. extractionextracted with EtOAc
  4. customThe reaction was then quenched with citric acid (2 mL, 10% w/v)
  5. extractionextracted with EtOAc (2×5 mL)
  6. concentrationconcentrated in vacuo
  7. customto give a crude residue, which
  8. customwas purified via reverse phase HPLC

Sources & evidence

ORD record
ord-9cb89145074d4fc19979b783de92c71a
Source dataset
uspto-grants-2014_08
Patent number
US08796258B2

Reaction notes

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