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

HRID 858633Notes

Reaction equation

HRID 858633 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.[Cl: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>[Cl:28][C:29]1[CH:30]=[N:31][C:32]2[N:33]([N:35]=[C:36]([CH2:38][CH:9]3[C:8](=[O:13])[O:7][C:6]([CH2:14][CH2:15][C:16]4[CH:21]=[CH:20][C:19]([C:22]5([C:25]#[N:26])[CH2:23][CH2:24]5)=[C:18]([F:27])[CH:17]=4)([CH:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[CH2:11][C:10]3=[O:12])[N:37]=2)[CH:34]=1

Participants

4

Reactant 2

HCID 587625546-Chloro-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehydeHCID 587627061-{4-[2-(2-Cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile

Product 1

HCID 112034471-(4-{2-[5-(6-Chloro-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl)-2-cyclopentyl-4,6-dioxo-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 6-chloro-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (365 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). The resultant oil was further purified by flash 509 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 the desired product as an oil. It was further purified by crystallization from ethyl acetate/hexanes to give a white powder (48.6 mg, 6%). 1H NMR (400 MHz, CDCl3) δ: 1.19–1.24 (m, 2 H), 1.39–1.61 (m, 10 H), 1.83–1.87 (m, 2 H), 2.25 (t, J=8.59 Hz, 1 H), 2.38 (d, J=17.94 Hz, 1 H), 2.54 (t, J=7.71 Hz, 2 H), 2.64 (d, J=17.94 Hz, 1 H), 3.98 (d, J=5.56 Hz, 2 H), 6.71–6.77 (m, 2 H), 7.06 (t, J=7.83 Hz, 1 H), 8.66 (s, 1 H), 8.73 (s, 1 H).

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)
  4. customThe resultant oil was further purified by flash 509 SiO2, 1:3->1:0 (93.5% ethyl acetate, 6% methanol, 0.5% acetic acid)

Sources & evidence

ORD record
ord-e646ae1d36b24d779bb76a5e063db128
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Reaction notes

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