Lithium Hydroxide → 4-(6-amino-5-(1-isopropyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)-2-methylbenzoic acid

HRID 632476Notes

Reaction equation

HRID 632476 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].Br[C:8]1[CH:9]=[C:10]([C:15]2[N:16]=[N:17][N:18]([CH:20]([CH3:22])[CH3:21])[CH:19]=2)[C:11]([NH2:14])=[N:12][CH:13]=1.C[O:24][C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][C:28]=1[CH3:36])=[O:26].[Li+].[OH-]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:14][C:11]1[N:12]=[CH:13][C:8]([C:30]2[CH:31]=[CH:32][C:27]([C:25]([OH:26])=[O:24])=[C:28]([CH3:36])[CH:29]=2)=[CH:9][C:10]=1[C:15]1[N:16]=[N:17][N:18]([CH:20]([CH3:22])[CH3:21])[CH:19]=1

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 10796Cesium carbonateHCID 22171598(4-(Methoxycarbonyl)-3-methylphenyl)boronic acidHCID 902731555-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine

Product 1

HCID 902731784-(6-amino-5-(1-isopropyl-1H-1,2,3-triazol-4-yl)pyridin-3-yl)-2-methylbenzoic acidYield 58.65%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Cs2CO3 (1.03 g, 3.18 mmol) was added to a solution of 5-bromo-3-(1-isopropyl-1H-[1,2,3]triazol-4-yl)-pyridin-2-ylamine (300 mg, 1.06 mmol) and (4-(methoxycarbonyl)-3-methylphenyl)boronic acid (247 mg, 1.27 mmol) in dioxane: water (10 mL: 5 mL), degassed the reaction mixture for 10 min with nitrogen. Then added Pd(PPh3)4 (61 mg, 0.053 mmol), degassed the reaction mixture for additional 10 min with nitrogen, the reaction mixture was heated to 120° C. in microwave for 1 h. LiOH (222 mg, 5.30 mmol) was added to the reaction mixture and, heated to 100° C. for 3 h. Then diluted with water (50 mL) and extracted with ethyl acetate (2×30 mL). Aqueous layer was acidified with 2N HCl, pH was adjusted to 6 and extracted with ethyl acetate (2×30 mL). Dried over Na2SO4 and concentrated under reduced pressure to afford 210 mg of (Yield: 58.65%) the title compound as a white solid.

Workup

  1. customwater (10 mL: 5 mL), degassed the reaction mixture for 10 min with nitrogen
  2. temperatureheated to 100° C. for 3 h
  3. extractionextracted with ethyl acetate (2×30 mL)
  4. extractionextracted with ethyl acetate (2×30 mL)
  5. dry with materialDried over Na2SO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-478241e239c640ecae7a191d59be9ab3
Source dataset
uspto-grants-2016_04
Patent number
US09321748B2

Reaction notes

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