5,7-Dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde → 2-[4-[2-[2-cyclopentyl-5-[(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl]-4-hydroxy-6-oxo-3H-pyran-2-yl]ethyl]-2-fluoro-phenyl]-2-methyl-propanenitrile

HRID 1453085Notes

Reaction equation

HRID 1453085 reaction equation
[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH3:26])([CH3:25])[C:23]#[N:24])=[C:18]([F:27])[CH:17]=3)[CH2:11][C:10](=[O:12])[CH2:9][C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:28][C:29]1[CH:34]=[C:33]([CH3:35])[N:32]2[N:36]=[C:37]([CH:39]=O)[N:38]=[C:31]2[N:30]=1>CO>[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH3:25])([CH3:26])[C:23]#[N:24])=[C:18]([F:27])[CH:17]=3)[CH2:11][C:10]([OH:12])=[C:9]([CH2:39][C:37]3[N:38]=[C:31]4[N:30]=[C:29]([CH3:28])[CH:34]=[C:33]([CH3:35])[N:32]4[N:36]=3)[C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 236352265,7-Dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehydeHCID 587624232-{4-[2-(2-cyclopentyl-4,6-dioxotetrahydro-2H-pyran-2-yl)ethyl]-2-fluorophenyl)-2-methylpropanenitrile

Product 1

HCID 547088342-[4-[2-[2-cyclopentyl-5-[(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl]-4-hydroxy-6-oxo-3H-pyran-2-yl]ethyl]-2-fluoro-phenyl]-2-methyl-propanenitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-{4-[2-(2-cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-2-methyl-propionitrile (0.40 g, 1.1 mmol) in MeOH (7 mL) was added 5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (0.19 g, 1.08 mmol) and borane-dimethylamine complex (76 mg, 1.3 mmol) and stirred at room temperature for 3 hours. The reaction was quenched with 10 mL saturated NH4Cl and 5 mL water. To this was added 20 mL CH2Cl2 and the pH of the aqueous phase was adjusted to 3. The layers were separated, and the aqueous layer was extracted with 3×30 mL 10% MeOH in CH2Cl2. The organic layers were combined, and dried over Na2SO4. After filtering off the solids, the liquid was concentrated by rotary evaporation to an oil. The oil was flash chromatographed, and the resulting product was further purified by preparatory HPLC. Yield: 28 mg, 5%. MS (ESI): 530 (M−H).

Workup

  1. customThe reaction was quenched with 10 mL saturated NH4Cl and 5 mL water
  2. additionTo this was added 20 mL CH2Cl2
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with 3×30 mL 10% MeOH in CH2Cl2
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtering off the solids
  7. concentrationthe liquid was concentrated by rotary evaporation to an oil
  8. customchromatographed
  9. customthe resulting product was further purified by preparatory HPLC

Sources & evidence

ORD record
ord-e8fadb4d2c3a44d9acfe4123cab41998
Source dataset
uspto-grants-2009_01
Patent number
US07473790B2

Reaction notes

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