Methanol → HCID 178430632, compound

HRID 537058Notes

Reaction equation

HRID 537058 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:12][C:11]([C:13]2[C:18]([CH3:19])=[CH:17][N:16]=[C:15]([NH2:20])[CH:14]=2)=[N:10][C:9]=1[C:21]1[N:25](COCC[Si](C)(C)C)[CH:24]=[N:23][N:22]=1.[CH:34]1([C:37](Cl)=[O:38])[CH2:36][CH2:35]1.CO>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:12][C:11]([C:13]2[C:18]([CH3:19])=[CH:17][N:16]=[C:15]([NH:20][C:37]([CH:34]3[CH2:36][CH2:35]3)=[O:38])[CH:14]=2)=[N:10][C:9]=1[C:21]1[NH:25][CH:24]=[N:23][N:22]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 77637Cyclopropanecarbonyl chlorideHCID 667495874-[5-(2-chlorophenyl)-4-(4-{[2-(trimethylsilyl)-ethoxy]methyl}-4H-1,2,4-triazol-3-yl)-1,3-oxazol-2-yl]-5-methylpyridin-2-amine

Product 1

HCID 178430632HCID 178430632, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-[5-(2-chlorophenyl)-4-(4-{[2-(trimethylsilyl)-ethoxy]methyl}-4H-1,2,4-triazol-3-yl)-1,3-oxazol-2-yl]-5-methylpyridin-2-amine (0.12 g, 0.25 mmol) and TEA (0.087 mL, 0.62 mmol) in DCM (2 mL) was allowed to stir at 0° C. for 20 min. To this mixture was added cyclopropanecarbonyl chloride (0.056 mL, 0.62 mmol). The reaction mixture was allowed to stir at 0° C. for 2 h and then MeOH (20 mL) was added. The mixture was allowed to stir at rt for 20 min and was then concentrated. MeOH (25 mL) and aqueous saturated NaHCO3 (4 mL) were added to the residue and the mixture was allowed to stir at rt overnight before NaOH (1M, 3 mL) was added. The reaction mixture was allowed to stir rt for 3 h and then concentrated. EtOAc (30 mL) was added to the residue and the mixture was allowed to stir at rt for 30 min. The mixture was filtered and the filtrate was concentrated. DCM (5 mL) and TFA (2 mL) were added to the residue and the mixture was allowed to stir at rt overnight. The reaction mixture was concentrated and purified by column chromatography to give N-{4-[5-(2-chlorophenyl)-4-(4H-1,2,4-triazol-3-yl)-1,3-oxazol-2-yl]-5-methylpyridin-2-yl}cyclopropanecarboxamide (Compound I-77) (0.025 g, 24%). LCMS (AA): m/z=421 (M+H).

Workup

  1. stirringto stir at 0° C. for 2 h
  2. stirringto stir at rt for 20 min
  3. concentrationwas then concentrated
  4. additionMeOH (25 mL) and aqueous saturated NaHCO3 (4 mL) were added to the residue
  5. stirringto stir at rt overnight before NaOH (1M, 3 mL)
  6. additionwas added
  7. stirringto stir rt for 3 h
  8. concentrationconcentrated
  9. additionEtOAc (30 mL) was added to the residue
  10. stirringto stir at rt for 30 min
  11. filtrationThe mixture was filtered
  12. concentrationthe filtrate was concentrated
  13. additionDCM (5 mL) and TFA (2 mL) were added to the residue
  14. stirringto stir at rt overnight
  15. concentrationThe reaction mixture was concentrated
  16. custompurified by column chromatography

Sources & evidence

ORD record
ord-f294d9bd6be94888a3f32512869c41c2
Source dataset
uspto-grants-2014_10
Patent number
US08859768B2

Reaction notes

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