Iodo benzene diacetate → 5,7-Dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde

HRID 2387171Notes

Reaction equation

HRID 2387171 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]2[N:9]=[C:10]([CH2:12][OH:13])[N:11]=[C:4]2[N:3]=1.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>C(Cl)Cl>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]2[N:9]=[C:10]([CH:12]=[O:13])[N:11]=[C:4]2[N:3]=1

Participants

4

Reactant 2

HCID 12217721Iodo benzene diacetate2×HCID 44141733(5,7-Dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methanol

Product 1

HCID 236352265,7-Dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 10 L reactor was sequentially charged CH2Cl2 (5.1 L), (5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methanol (680 g, 3.816 mol), and iodobenzene diacetate (1352 g, 4.197 mol). As the iodobenzene diacetate dissolves, there is a significant endotherm (typically down to 15-16° C.). The jacket was set to 23° C. The mixture was warmed to ambient temperature and Tempo (2,2,6,6-tetramethyl-1-piperidinyloxy, free radical, 43.75 g, 0.28 mol) added in a single charge. The reaction was stirred until 5% of the starting alcohol remained by HPLC. Once the starting material is adjudged to be less than about ˜5%, the over-oxidized product begins to be observed. Allowing the reaction to run to further completion leads to an overall diminished yield of the desired product. For this reaction, the desired reaction completion was reached in 2.75 h. MTBE (5.1 L) was then slowly charged to the reactor, causing the product to precipitate, and the slurry stirred for an additional 30 mins. The mixture was filtered, washed twice with 1:1 DCM/MTBE (2×1 L), and dried in a vacuum oven overnight at 50° C. to provide 500.3 g (74%) of 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde as an off-white solid. 1H NMR (300 MHz, d6-DMSO): 2.64 (s, 3), 2.78 (d, 3, J=0.8), 7.36 (d, 1, J=0.9), 10.13 (s, 1).

Workup

  1. customTo a 10 L reactor was sequentially charged
  2. customtypically down to 15-16° C.
  3. customwas set to 23° C
  4. additionTempo (2,2,6,6-tetramethyl-1-piperidinyloxy, free radical, 43.75 g, 0.28 mol) added in a single charge
  5. customthe reaction

Sources & evidence

ORD record
ord-176c7d6150db4926b25a117de26cc1c8
Source dataset
uspto-grants-2012_09
Patent number
US08268835B2

Reaction notes

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