1-{4-[2-(2-Cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile → {4-[2-(2-Cyclopentyl-4,6-dioxo-5-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile

HRID 1453083Notes

Reaction equation

HRID 1453083 reaction equation
[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4([C:25]#[N:26])[CH2:24][CH2:23]4)=[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.[N:28]1[N:32]2[CH:33]=[CH:34][CH:35]=[N:36][C:31]2=[N:30][C:29]=1[CH:37]=O>CO>[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4([C:25]#[N:26])[CH2:23][CH2:24]4)=[C:18]([F:27])[CH:17]=3)[CH2:11][C:10](=[O:12])[CH:9]([CH2:37][C:29]3[N:30]=[C:31]4[N:36]=[CH:35][CH:34]=[CH:33][N:32]4[N:28]=3)[C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 587627061-{4-[2-(2-Cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrileHCID 58764260[1,2,4]Triazolo[1,5-a]pyrimidine-2-carbaldehyde

Product 1

HCID 68865868{4-[2-(2-Cyclopentyl-4,6-dioxo-5-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1-{4-[2-(2-cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile (568 mg, 1.54 mmol) in anhydrous MeOH (6.0 mL) was treated with [1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (296 mg, 2.0 mmol), followed by borane-dimethylamine complex (118 mg, 2.0 mmol) at room temperature. The reaction was stirred for 1 hour and then was concentrated to an oil. The oil was purified by flash chromatography (50 g SiO2, 70% ethyl acetate, 6% methanol, 0.5% acetic acid, 23.5% hexanes) to give the desired product as an oil. It was further purified by crystallization from ethyl acetate/hexanes to give a white powder (142 mg, 18%). 1H NMR (400 MHz, CDCl3) δ: 1.11-1.18 (m, 2H), 1.31-1.52 (m, 10H), 1.75-1.80 (m, 2H), 2.16 (t, J=8.84 Hz, 1H), 2.34 (d, J=17.68 Hz, 1H), 2.46 (t, J=7.83 Hz, 2H), 2.59 (d, J=17.94 Hz, 1H), 3.94 (d, J=3.79 Hz, 2H), 6.62-6.70 (m, 2H), 6.97 (t, J=7.83 Hz, 1H), 7.02-7.04 (m, 1H), 6.82-6.85 (m, 2H).

Workup

  1. customfollowed by borane-dimethylamine complex (118 mg, 2.0 mmol) at room temperature
  2. concentrationwas concentrated to an oil
  3. customThe oil was purified by flash chromatography (50 g SiO2, 70% ethyl acetate, 6% methanol, 0.5% acetic acid, 23.5% hexanes)

Sources & evidence

ORD record
ord-3b401495c1b04e59b2151ca00293fd40
Source dataset
uspto-grants-2009_01
Patent number
US07473790B2

Reaction notes

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