6-Ethyl[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxaldehyde → HCID 57477231, compound

HRID 858699Notes

Reaction equation

HRID 858699 reaction equation
[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[C:20]([F:22])[C:19]([C:23]([CH3:27])([CH3:26])[C:24]#[N:25])=[C:18]([F:28])[CH:17]=3)[CH2:11][C:10]([OH:12])=[CH:9][C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:29]([C:31]1[CH:32]=[N:33][C:34]2[N:35]([N:37]=[C:38]([CH:40]=O)[N:39]=2)[CH:36]=1)[CH3:30]>CO>[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[C:20]([F:22])[C:19]([C:23]([CH3:26])([CH3:27])[C:24]#[N:25])=[C:18]([F:28])[CH:17]=3)[CH2:11][C:10]([OH:12])=[C:9]([CH2:40][C:38]3[N:39]=[C:34]4[N:33]=[CH:32][C:31]([CH2:29][CH3:30])=[CH:36][N:35]4[N:37]=3)[C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 601250186-Ethyl[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxaldehydeHCID 68866297HCID 68866297, compound

Product 1

HCID 57477231HCID 57477231, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-{4-[2-(2-Cyclopentyl-4-hydroxy-6-oxo-3,6-dihydro-2H-pyran-2-yl)-ethyl]-2,6-difluoro-phenyl}-2-methyl-propionitrile (272 mg, 0.7 mmol) in anhydrous MeOH (1.5 mL) was treated with 6-ethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (324 mg, 2.0 mmol), followed by borane-dimethylamine complex (191.7 mg, 1.05 mmol) at room temperature. The reaction was stirred for 12 hours. The precipitate was removed by filtration, and the filtrate was concentrated to a crude oil. The crude oil was purified by flash chromatography (25 g SiO2, 1:3:1:0 (93.5% ethyl acetate, 6% methanol, 0.5% acetic acid): (81.5% hexanes, 12% ethyl acetate, 6% methanol, 0.5% acetic acid)) to give product as an oil. It was further purified by preparatory HPLC. Yield: 19.0 mg, 8.0%. 1H NMR (CDCl3) δ: 1.37 (t, J=3.75 Hz, 3H)), 1.48–1.75 (m, 8H), 1.84 (s, 6H), 1.91–2.02 (m, 2H), 2.32–2.49 (m, 3H), 2.61–2.70 (m, 2H), 2.79–2.86 (m, 2H), 4.10 (s, 2H), 6.69 (d, J=10.86 Hz, 2H), 8.62 (s, 1H), 8.73 (s, 1H). MS (ESI): 548 (M−H).

Workup

  1. customfollowed by borane-dimethylamine complex (191.7 mg, 1.05 mmol) at room temperature
  2. customThe precipitate was removed by filtration
  3. concentrationthe filtrate was concentrated to a crude oil
  4. customThe crude oil was purified by flash chromatography (25 g SiO2, 1:3:1:0 (93.5% ethyl acetate, 6% methanol, 0.5% acetic acid): (81.5% hexanes, 12% ethyl acetate, 6% methanol, 0.5% acetic acid))
  5. customto give product as an oil
  6. customIt was further purified by preparatory HPLC

Sources & evidence

ORD record
ord-1bbc0065ab5849b198ac8a202cf9c9b4
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Reaction notes

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