Hydrochloric Acid → 6-[2-(3-Chloro-4-isopropoxy-phenyl)-ethyl]-6-cyclopentyl-3-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl)-4-hydroxy-5,6-dihydro-pyran-2-one

HRID 1453177Notes

Reaction equation

HRID 1453177 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:12][CH2:13][C:14]2([CH:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[O:19][C:18](=[O:20])[CH2:17][C:16](=[O:21])[CH2:15]2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[CH3:27][C:28]1[CH:33]=[C:32]([CH3:34])[N:31]2[N:35]=[C:36]([CH:38]=O)[N:37]=[C:30]2[N:29]=1.N(C)C.Cl>CO.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:12][CH2:13][C:14]2([CH:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[O:19][C:18](=[O:20])[C:17]([CH2:38][C:36]3[N:37]=[C:30]4[N:29]=[C:28]([CH3:27])[CH:33]=[C:32]([CH3:34])[N:31]4[N:35]=3)=[C:16]([OH:21])[CH2:15]2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 167287396-[2-(3-Chloro-4-isopropoxy-phenyl)ethyl]-6-cyclopentyl-tetrahydropyran-2,4-dioneHCID 236352265,7-Dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde

Product 1

HCID 587622326-[2-(3-Chloro-4-isopropoxy-phenyl)-ethyl]-6-cyclopentyl-3-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl)-4-hydroxy-5,6-dihydro-pyran-2-oneYield 24%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

6-[2-(3-Chloro-4-isopropoxy-phenyl)-ethyl]-6-cyclopentyl-dihydro-pyran-2,4-dione (0.3 g, 0.79 mmol) and 5,7-Dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (0.17 g, 0.95 mmol, described in Step 3 of example B(75)) were dissolved in 3:1 MeOH/CH2Cl2 (4 mL). To this suspension, Me2NH.BH3 (0.07 g, 1.19 mmol) was added as a solid from top. After stirring 1 h at room temperature, the reaction mixture became clear and it was stirred for an additional 5 hours. After this time, 1 M HCl (1 mL) was added and the reaction stirred for 30 minutes at room temperature, the solvent was the evaporated to half the volumen and extracted 3 times with 10% MeOH/CH2Cl2 (10 mL). The organic phase was dried over MgSO4 and evaporated. The residue purified by flash column chromatography (80% EtOAc in hexanes) to eliminate unreacted pyrone and reduced 5,7-Dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde, then 3% MeOH/CH2Cl2 to give the product (0.1 g, 24%) as a white solid. 1H NMR (DMSO-d6): δ 1.14 (d, J=6.3, 6H), 1.4-1.53 (m, 8H), 1.7-1.75 (m, 2H), 1.95-1.98 (m, 1H), 2.35-2.44 (m, 8H), 3.19 (s, 2H), 3.57 (d, J=16 Hz, 1H), 3.69 (d, J=16 Hz, 1H), 4.41-4.47 (m, 1H), 6.91-6.93 (s, 1H), 7-7.07 (m, 2H), 7.10 (d, J=2.0, 1H), 10.7 (brs, 1H). Anal. Calcd. For C29H35N4O4: C, 64.61; H, 6.54; N, 10.39. Found: C, 64.30; H, 6.81; N, 10.35. ESIMS (MH+): 540

Workup

  1. additionBH3 (0.07 g, 1.19 mmol) was added as a solid from top
  2. stirringit was stirred for an additional 5 hours
  3. stirringthe reaction stirred for 30 minutes at room temperature
  4. customevaporated to half the volumen
  5. extractionextracted 3 times with 10% MeOH/CH2Cl2 (10 mL)
  6. dry with materialThe organic phase was dried over MgSO4
  7. customevaporated
  8. customThe residue purified by flash column chromatography (80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-e879d0a63f2943eba2e25932e08f0bf2
Source dataset
uspto-grants-2009_01
Patent number
US07473790B2

Reaction notes

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