Diisopropylethylamine → (S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone

HRID 1423156Notes

Reaction equation

HRID 1423156 reaction equation
[CH2:1]([C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][C:29]1[NH:33][N:32]=[C:31]([CH2:34][C:35](O)=[O:36])[N:30]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[CH2:1]([C@H:8]1[CH2:9][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:11][CH2:12][N:13]1[C:35](=[O:36])[CH2:34][C:31]1[N:30]=[C:29]([CH3:28])[NH:33][N:32]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 70194772-(3-methyl-1H-1,2,4-triazol-5-yl)acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16725642(S)-3-Benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine2×

Product 1

HCID 58189118(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanoneYield 65%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

A solution of 3-benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine (Example 2, Compound 90) (100 mg, 0.273 mmol), in CH2Cl2:DMF (1:1, 3 mL), then treated with (5-methyl-1H[1,2,4]triazol-3-yl)-acetic acid (50.0 mg, 0.355 mmol), followed by the addition of diisopropylethylamine μL, 0.819 mmol) and HATU (135 mg, 0.355 mmol). (100 The reaction stirred at room temperature for 8 h. The solution was washed with a saturated aqueous solution of NaHCO3 (10 mL) followed by brine (10 mL). The organic portion was dried over MgSO4, filtered and evaporated to an oil which was purified by silica gel flash chromatography with 5% then 10% MeOH/EtOAc as eluant to afford product as a colorless solid (86 mg, 65%). 1H NMR (CDCl3) 1.50-1.65 (m, 4H), 1.70-2.00 (m, 6H), 2.42 (s, 3H), 2.46 (s, 2H), 2.61-2.99 (m, 2H), 3.21-3.51 (m, 3H), 3.72-3.99 (m, 4H), 4.62-4.79 (m, 1H), 6.38-6.60 (m, 2H), 6.70-6.82 (m, 1H), 7.20-7.39 (m, 5H). 13C NMR 44.8 (CH2), 53.5 (CH2), 54.8 (CH), 55.3 (CH2), 56.6 (CH2), 63.2 (CH2), 105.4 (CH), 127.1 (CH), 128.2 (CH), 129.0 (CH), 130.0 (CH), 138.0, 139.8 (CH). LC/MS (Method B) 3.32 min, [M+1]+ 490.2.

Workup

  1. washThe solution was washed with a saturated aqueous solution of NaHCO3 (10 mL)
  2. dry with materialThe organic portion was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated to an oil which
  5. customwas purified by silica gel flash chromatography with 5%

Sources & evidence

ORD record
ord-c138d17521d7454f9677317c6df9945f
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

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