Ethylene Glycol → HCID 178434333, compound

HRID 2070916Notes

Reaction equation

HRID 2070916 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([NH:11][C:12]3[N:28]=[C:15]4[CH:16]=[CH:17][CH:18]=[C:19]([CH2:20]N5C=CC=CC5=O)[N:14]4[N:13]=3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.O.NN.[OH-].[K+].[CH2:34]([OH:37])[CH2:35]O>O>[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([NH:11][C:12]3[N:28]=[C:15]4[CH:16]=[CH:17][CH:18]=[C:19]([CH2:20][C:9]5[CH:10]=[CH:2][N:3]=[C:34]([OH:37])[CH:35]=5)[N:14]4[N:13]=3)=[CH:8][CH:9]=2)[NH:4][N:3]=1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 178434335HCID 178434335, compound

Product 1

HCID 178434333HCID 178434333, compoundYield 4.77%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
190 °C

Procedure

4-((2-(3-methyl-1H-indazol-6-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-ylmethyl)pyridin-2(1H)-one. To a solution/suspension of (2-methoxypyridin-4-yl)(2-(3-methyl-1H-indazol-6-ylamino)-[1,2,4]triazolo[1,5-c]pyridin-5-yl)methanone (400 mg, 0.847 mmol), in a 50 mL pressure vial, hydrazine hydrate (1.232 mL, 25.4 mmol), and potassium hydroxide (1188 mg, 21.17 mmol) were added followed by ethylene glycol (10 mL). The reaction mixture was heated to 190° C., and was left to stir overnight, then checked by LCMS. Once the reaction was complete, water was added to the crude mixture and the product was extracted with ethyl acetate three times. The organics were washed with brine and dried over sodium sulfate. The crude was purified on semi-preparative HPLC (20-100% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, 20 min). The fractions containing the product were loaded on a strata-X column to remove trifluoroacetic acid, then methanol was evaporated in vacuo. 4-((2-(3-methyl-1H-indazol-6-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)methyl)pyridin-2-ol (15 mg, 0.040 mmol, 4.77% yield) was obtained as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 12.38 (s, 1H), 11.70 (br s, 1H), 9.76 (s, 1H), 8.07 (d, J=1.17 Hz, 1H), 7.56-7.65 (m, 1H), 7.49-7.55 (m, 2H), 7.34 (d, J=6.64 Hz, 1H), 7.08 (td, J=1.56, 7.81 Hz, 2H), 6.53 (d, J=0.78 Hz, 1H), 6.19 (dd, J=1.56, 6.64 Hz, 1H), 4.31 (s, 2H), 2.43 (s, 3H); MS (ESI): m/z 371.7 [M+1]+.

Workup

  1. waitwas left
  2. extractionthe product was extracted with ethyl acetate three times
  3. washThe organics were washed with brine
  4. dry with materialdried over sodium sulfate
  5. customThe crude was purified on semi-preparative HPLC (20-100% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, 20 min)
  6. additionThe fractions containing the product
  7. customto remove trifluoroacetic acid
  8. custommethanol was evaporated in vacuo

Sources & evidence

ORD record
ord-c33143bfe2cd47dcae8266ff9ed79475
Source dataset
uspto-grants-2012_10
Patent number
US08299056B2

Reaction notes

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