4-Nitrophenyl chloroformate → HCID 21073537, compound

HRID 1373618Notes

Reaction equation

HRID 1373618 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([NH2:28])=[N:5][C:6]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=3[Cl:27])[CH2:16][CH2:15]2)=[CH:7][CH:8]=1.Cl[C:30](OC1C=CC([N+]([O-])=O)=CC=1)=[O:31].[Li+].CC([N-]C(C)C)C>C1COCC1>[Cl:27][C:21]1[C:22]([Cl:26])=[CH:23][CH:24]=[CH:25][C:20]=1[N:17]1[CH2:16][CH2:15][N:14]([CH2:13][CH2:12][CH2:11][CH2:10][O:9][C:6]2[CH:7]=[CH:8][C:3]3[CH2:2][NH:1][C:30](=[O:31])[NH:28][C:4]=3[N:5]=2)[CH2:19][CH2:18]1

Participants

5

Reactant 3

HCID 821294-Nitrophenyl chloroformateHCID 2724682Lithium diisopropylamideHCID 21073298HCID 21073298, compound

Product 1

HCID 21073537HCID 21073537, compoundYield 25.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-aminomethyl-6-{4-[4-(2,3-dichloro-phenyl)-piperazin-1-yl]-butoxy}-pyridin-2-ylamine (0.260 g, 0.61 mmol) in THF (10 mL) was treated with 4-nitrophenyl chloroformate (0.160 g, 0.79 mmol). The mixture was stirred at room temperature for 30 minutes, then cooled to 0° C. and treated with LDA (0.9 mL, 3.8 mmol, 2.0 M in heptane/THF/ethylbenzene). The brown mixture was stirred at room temperature for 1 hour, then quenched with water and extracted with EtOAc. The organic extracts were washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by preparative thin layer chromatography (10% MeOH/EtOAc) to afford the title compound as a light yellow solid (0.071 g, 25%). mp 166–167° C.; 1 H NMR (400 MHz, CDCl3): δ 7.25 (s, 1H), 7.19–7.14 (m, 2H), 7.14–7.09 (br s, 1H), 6.99–6.94 (m, 1H), 6.32 (d, 1H), 5.57–5.51 (br s, 1H), 4.45 (s, 2H), 4.24 (t, 2H), 3.16–3.02 (m, 4H), 2.75–2.58 (m, 4H), 2.49 (t, 2H), 1.84–1.64 (m, 4H). MS ES: m/z=450.03, 452.02.

Workup

  1. temperaturecooled to 0° C.
  2. stirringThe brown mixture was stirred at room temperature for 1 hour
  3. customquenched with water
  4. extractionextracted with EtOAc
  5. washThe organic extracts were washed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by preparative thin layer chromatography (10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-252be87dcd8447afbe9718f4d3cd055c
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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