Lithium Hydroxide → 5-([1,2,4]Triazolo[4,3-a]pyridin-6-yl)-6-(4-fluorophenyl)imidazo[2,1-b]oxazole

HRID 1711794Notes

Reaction equation

HRID 1711794 reaction equation
F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[CH:18]=[N:19][C:20]([NH:23][NH2:24])=[CH:21][CH:22]=1)[CH:14]=[CH:13][O:12]2.F[C:26]1C=CC(C2N=C3N(C=2)C=CO3)=CC=1.C1C(=O)N(I)C(=O)C1.FC1C=CC(B(O)O)=CN=1.NN.O=CC(OCC)=O.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.[Li+].[OH-]>CO.O>[N:23]1[N:24]=[CH:26][N:19]2[CH:18]=[C:17]([C:16]3[N:15]4[C:11]([O:12][CH:13]=[CH:14]4)=[N:10][C:9]=3[C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][CH:2]=3)[CH:22]=[CH:21][C:20]=12

Participants

11

Reactant 8

HCID 3939Lithium HydroxideHCID 9321HydrazineHCID 70211Ethyl oxoacetateHCID 120273N-IodosuccinimideHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 12217721Iodo benzene diacetateHCID 574336106-(4-Fluorophenyl)-imidazo[2,1-b]oxazoleHCID 594578146-(2,4-Difluorophenyl)-5-(6-hydrazinylpyridin-3-yl)imidazo[2,1-b]oxazole

Product 1

HCID 594578155-([1,2,4]Triazolo[4,3-a]pyridin-6-yl)-6-(4-fluorophenyl)imidazo[2,1-b]oxazoleYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

The 6-(2,4-difluorophenyl)-5-(6-hydrazinylpyridin-3-yl)imidazo[2,1-b]oxazole (0.20 g, 0.65 mmol; prepared using A from 6-(4-fluorophenyl)-imidazo[2,1-b]oxazole [prepared according to WO2004110990A2, Example 1, Steps 1-3] with NIS, C with 2-fluoropyridine-5-boronic acid [Asymchem], D with hydrazine) and ethyl 2-oxoacetate (0.65 mL, 9.7 mmol) were dissolved in MeOH (5.0 mL) and heated to about 65° C. for about 1 h. The MeOH was evaporated and then DCM (5 mL) was added followed by iodobenzene diacetate (0.53 g, 1.6 mmol). The reaction was stirred for about 15 min then the DCM was evaporated and the resulting solid was triturated with Et2O. The solid was dissolved in 1,4-dioxane (10 mL) and LiOH (0.060 g, 2.4 mmol) dissolved in water (2 mL) was added drop-wise followed by heating to about 50° C. for about 30 min. The 1,4-dioxane was evaporated and the pH was adjusted to about 1 with 1N HCl. The resulting precipitate was filtered and washed with water (about 10 mL) and dried in a vacuum oven to give the title compound (0.31 g, 80%): LC/MS (Table 1, Method a) Rt=1.88 min; MS m/z: 320.1 (M+H)+.

Workup

  1. customprepared
  2. customThe MeOH was evaporated
  3. additionDCM (5 mL) was added
  4. customthe DCM was evaporated
  5. customthe resulting solid was triturated with Et2O
  6. dissolutionThe solid was dissolved in 1,4-dioxane (10 mL)
  7. additionwas added drop-wise
  8. temperatureby heating to about 50° C. for about 30 min
  9. customThe 1,4-dioxane was evaporated
  10. filtrationThe resulting precipitate was filtered
  11. washwashed with water (about 10 mL)
  12. customdried in a vacuum oven

Sources & evidence

ORD record
ord-48949c59adad4c979d002ebc935fc6af
Source dataset
uspto-grants-2010_09
Patent number
US07790741B2

Reaction notes

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