5-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine → HCID 178517536, compound

HRID 2070908Notes

Reaction equation

HRID 2070908 reaction equation
[NH2:1][C:2]1[N:20]=[C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([C:10]([C:12]3[CH:17]=[CH:16][N:15]=[C:14]([O:18]C)[CH:13]=3)=O)[N:4]2[N:3]=1.BrC1N2N=C(N)N=C2C=CC=1.[CH2:32]([Li])[CH2:33][CH2:34][CH3:35].CO[N:39]([CH3:50])[C:40](=[O:49])[C:41]1C=CN=C(OC)[CH:42]=1>O1CCCC1>[OH:18][C:14]1[CH:13]=[C:12]([CH2:10][C:9]2[N:4]3[N:3]=[C:2]([NH:1][C:33]4[CH:34]=[C:35]5[C:41](=[CH:42][CH:32]=4)[C:40](=[O:49])[NH:39][CH2:50]5)[N:20]=[C:5]3[CH:6]=[CH:7][CH:8]=2)[CH:17]=[CH:16][N:15]=1

Participants

6

Reactant 4

HCID 252159395-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amineHCID 53216603N,2-Dimethoxy-N-methylpyridine-4-carboxamideHCID 68588825HCID 68588825, compoundHCID 178418339Butyllithium

Product 1

HCID 178517536HCID 178517536, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(2-Amino-[1,2,4]triazolo[1,5-a]pyridin-5-yl)(2-methoxypyridin-4-yl)methanone. 5-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine (10 g, 46.9 mmol) was suspended in anhydrous tetrahydrofuran (300 mL) and cooled to −78° C. n-Butyl lithium (64.5 mL, 103 mmol) was added over 30 minutes and the solution was allowed to stir for 1 h (brown suspension). N,2-dimethoxy-N-methylisonicotinamide (9.21 g, 46.9 mmol) dissolved in tetrahydrofuran (50 mL, dried over molecular sieves) was added dropwise via syringe (brown suspension). The reaction was stirred for 1 h and allowed to slowly warm to room temperature for 3 h (reaction became a clear solution as it warmed up to room temperature). LCMS analysis showed the desired product. The reaction was quenched by dropwise addition of water (20 mL) and then neutralized with aqueous hydrochloric acid to pH=7. Flash chromatography (30-100% ethyl acetate in hexane) gave the desired product as a light yellow solid (6.5 g, 24.14 mmol, 51.4% yield). MS (ESI) m/z 270.2 [M+1]+.

Workup

  1. additionwas added over 30 minutes
  2. additionwas added dropwise via syringe (brown suspension)
  3. stirringThe reaction was stirred for 1 h
  4. customreaction
  5. temperaturewarmed up to room temperature)

Sources & evidence

ORD record
ord-794c17691e4c47f9a001740f2b5da6ca
Source dataset
uspto-grants-2012_10
Patent number
US08299056B2

Reaction notes

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