Diisopropylethylamine → HCID 90311805, compound

HRID 716191Notes

Reaction equation

HRID 716191 reaction equation
Cl.[CH3:2][C@H:3]1[CH2:8][NH:7][C@@H:6]([CH3:9])[CH2:5][N:4]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].Cl[C:18]1[CH:23]=[CH:22][N:21]=[CH:20][C:19]=1[N+:24]([O-:26])=[O:25].CCN(C(C)C)C(C)C>CC(O)C>[CH3:2][C@H:3]1[CH2:8][N:7]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][C:19]=2[N+:24]([O-:26])=[O:25])[C@@H:6]([CH3:9])[CH2:5][N:4]1[C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11]

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 27357814-Chloro-3-nitropyridineHCID 53484922HCID 53484922, compound

Product 1

HCID 90311805HCID 90311805, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
85 °C

Procedure

(2S,5S)-tert-butyl 2,5-dimethyl-4-(3-nitropyridin-4-yl) piperazine-1-carboxylate. To a solution of (2S,5S)-tert-butyl 2,5-dimethylpiperazine-1-carboxylate hydrochloride (1.17 g, 4.67 mmol, Acesys Pharmatech, A1653, Sample ID 119-99-18) in 2-Propanol (20 mL) was added 4-chloro-3-nitropyridine (1.11 g, 7.00 mmol, Alfa Aesar, Ward Hill, Mass.) and DIPEA (4.06 mL, 23.33 mmol). The mixture was heated and stirred at 85° C. for 2 h. Additional DIPEA (0.81 mL, 4.67 mmol) was added and the heat was raised to 90° C. The mixture was stirred at this temperature for 18 h. The mixture was then cooled to RT and concentrated. The residue was diluted with EtOAc (150 mL) and washed with water (15 mL) followed by brine (15 mL) and then dried over MgSO4. The crude material was purified by silica gel chromatography (30-70% EtOAc in hexanes) to afford (2S,5S)-tert-butyl 2,5-dimethyl-4-(3-nitropyridin-4-yl)piperazine-1-carboxylate (918 mg, 2.73 mmol, 59% yield) as a yellow solid. MS (ESI, pos. ion) m/z: 337.1 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.82 (s, 1 H), 8.38 (d, J=5.9 Hz, 1 H), 6.99 (d, J=6.1 Hz, 1 H), 4.12 (dd, J=14.0, 4.4 Hz, 1 H), 3.99-4.07 (m, 1 H), 3.94 (dt, J=10.8, 5.5 Hz, 1 H), 3.23 (dd, J=13.5, 9.4 Hz, 1 H), 2.98 (dd, J=14.1, 10.8 Hz, 1 H), 2.77 (dd, J=13.5, 5.7 Hz, 1 H), 1.46 (s, 9 H), 1.16 (d, J=6.3 Hz, 3 H), 1.13 (d, J=6.1 Hz, 3 H).

Workup

  1. temperatureThe mixture was heated
  2. temperaturethe heat was raised to 90° C
  3. stirringThe mixture was stirred at this temperature for 18 h
  4. temperatureThe mixture was then cooled to RT
  5. concentrationconcentrated
  6. additionThe residue was diluted with EtOAc (150 mL)
  7. washwashed with water (15 mL)
  8. dry with materialdried over MgSO4
  9. customThe crude material was purified by silica gel chromatography (30-70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-540cab413eab47a99c5823dcdde948f2
Source dataset
uspto-grants-2015_11
Patent number
US09187486B2

Reaction notes

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