6-Methyl-[1,2,4]triazolo[1,5-A]pyrimidine-2-carbaldehyde → 2-[4-({2-cyclopentyl-4-hydroxy-5-[(6-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl]-6-oxo-3,6-dihydro-2H-pyran-2-yl}methoxy)-2-fluorophenyl]-2-methylpropanenitrile

HRID 858852Notes

Reaction equation

HRID 858852 reaction equation
[CH:1]1([C:6]2([CH2:14][O: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:30]=[N:31][C:32]2[N:33]([N:35]=[C:36]([CH:38]=O)[N:37]=2)[CH:34]=1>CO>[CH:1]1([C:6]2([CH2:14][O: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]([CH2:38][C:36]3[N:37]=[C:32]4[N:31]=[CH:30][C:29]([CH3:28])=[CH:34][N:33]4[N:35]=3)[C:8](=[O:13])[O:7]2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 2

HCID 587626196-Methyl-[1,2,4]triazolo[1,5-A]pyrimidine-2-carbaldehydeHCID 601250172-[4-(2-Cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-ylmethoxy)-2-fluoro-phenyl]-2-methyl-propionitrile

Product 1

HCID 574772252-[4-({2-cyclopentyl-4-hydroxy-5-[(6-methyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl]-6-oxo-3,6-dihydro-2H-pyran-2-yl}methoxy)-2-fluorophenyl]-2-methylpropanenitrileYield 32.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-[4-(2-Cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-ylmethoxy)-2-fluoro-phenyl]-2-methyl-propionitrile (200 mg, 0.54 mmol) in anhydrous MeOH (4.0 mL) was treated with 6-Methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (140 mg, 0.86 mmol), followed by borane-dimethylamine complex (47 mg, 0.8 mmol) at room temperature. The reaction was stirred for 5 hours before it was quenched by the addition of 0.5N HCl (25 mL). The mixture was extracted with 10% MeOH in CH2Cl2 (3×10 mL) and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by crystallization from EtOAc/Hexanes to give the product as a white solid (91 mg, 32% yield). 1H NMR (300 MHz, DMSO-d6) δ: 1.67 (m, 8 H), 1.70 (s, 6 H), 2.38 (s, 3 H), 2.55 (m, 1 H), 2.77 (m, 2 H), 3.77 (m, 2 H), 4.12 (m, 1 H), 4.44 (m, 1 H), 6.97 (m 2 H), 7.35 (m, 1 H), 8.69 (s, 1 H), 9.03 (s, 1 H), 10.98 (brs, 1 H).

Workup

  1. customfollowed by borane-dimethylamine complex (47 mg, 0.8 mmol) at room temperature
  2. customwas quenched by the addition of 0.5N HCl (25 mL)
  3. extractionThe mixture was extracted with 10% MeOH in CH2Cl2 (3×10 mL)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by crystallization from EtOAc/Hexanes

Sources & evidence

ORD record
ord-feac88f76aaf434890de9d292453475b
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Reaction notes

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