Diisopropylethylamine → (S)-1-{1-[(4-chloro-2-cyanoquinolin-7-yl)methyl]-1H-1,2,3-triazol-4-yl}-1-(trifluoromethyl)propyl 4-nitrobenzoate

HRID 2422538Notes

Reaction equation

HRID 2422538 reaction equation
[N:1]([CH2:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([Cl:17])=[CH:10][C:11]([C:15]#[N:16])=[N:12]2)=[CH:7][CH:6]=1)=[N+:2]=[N-:3].[N+:18]([C:21]1[CH:38]=[CH:37][C:24]([C:25]([O:27][C:28]([CH2:35][CH3:36])([C:31]([F:34])([F:33])[F:32])[C:29]#[CH:30])=[O:26])=[CH:23][CH:22]=1)([O-:20])=[O:19].C(N(C(C)C)CC)(C)C>C1COCC1.C(OCC)(=O)C.[Cu](I)I>[N+:18]([C:21]1[CH:22]=[CH:23][C:24]([C:25]([O:27][C@@:28]([C:29]2[N:3]=[N:2][N:1]([CH2:4][C:5]3[CH:14]=[C:13]4[C:8]([C:9]([Cl:17])=[CH:10][C:11]([C:15]#[N:16])=[N:12]4)=[CH:7][CH:6]=3)[CH:30]=2)([C:31]([F:32])([F:33])[F:34])[CH2:35][CH3:36])=[O:26])=[CH:37][CH:38]=1)([O-:20])=[O:19]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 597748703-(Trifluoromethyl)pent-1-YN-3-YL 4-nitrobenzoateHCID 597748847-(Azidomethyl)-4-chloroquinoline-2-carbonitrile

Product 1

HCID 66790930(S)-1-{1-[(4-chloro-2-cyanoquinolin-7-yl)methyl]-1H-1,2,3-triazol-4-yl}-1-(trifluoromethyl)propyl 4-nitrobenzoate

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-(azidomethyl)-4-chloroquinoline-2-carbonitrile (560 mg, 2.3 mmol) and 1-ethyl-1-(trifluoromethyl)prop-2-yn-1-yl 4-nitrobenzoate (S-isomer, 728 mg, 2.42 mmol) in THF (18 mL) was added diisopropylethylamine (2.0 mL, 11.5 mmol) followed by copper iodide (655 mg, 3.45 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with a sat. sol. of NH4Cl, Brine and dried over anhydrous MgSO4. The solvent was removed under reduced pressure, and the resulting crude product was purified by flash chromatography (eluting solvent: 5% acetone in CH2Cl2) to afford the title compound. 1H NMR (400 MHz, acetone-d6): δ 8.55 (s, 1H), 8.45 (d, 2H), 8.37 (d, 1H), 8.30 (d, 2H), 8.22 (s, 1H), 8.07 (s, 1H), 7.90 (d, 1H), 6.05 (s, 2H), 3.05 (m, 1H), 2.85 (m, 1H), 1.15 (t, 3H).

Workup

  1. washwashed with a sat. sol. of NH4Cl, Brine
  2. dry with materialdried over anhydrous MgSO4
  3. customThe solvent was removed under reduced pressure
  4. customthe resulting crude product was purified by flash chromatography (eluting solvent: 5% acetone in CH2Cl2)

Sources & evidence

ORD record
ord-8dc0034b807946dcacd09bd7f1c9a81e
Source dataset
uspto-grants-2011_06
Patent number
US07960409B2

Reaction notes

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