Pyrrolidine → HCID 67057879, compound

HRID 2361692Notes

Reaction equation

HRID 2361692 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([N:14]3[CH2:17][CH:16]([O:18][C:19]4[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[C:21]([CH3:28])[CH:20]=4)[CH2:15]3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[CH3:29]C(N(C)C)=O.N1CCCC1>CN(C=O)C>[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([N:14]3[CH2:17][CH:16]([O:18][C:19]4[CH:20]=[C:21]5[C:22](=[CH:23][CH:24]=4)[NH:25][CH:29]=[CH:28]5)[CH2:15]3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 31374DimethylacetamideHCID 58243372HCID 58243372, compound

Product 1

HCID 67057879HCID 67057879, compoundYield 72.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
130 °C

Procedure

To a stirred solution of 1-cyclobutyl-4-{[3-(3-methyl-4-nitrophenoxy)azetidin-1-yl]carbonyl}-1,4-diazepane (40 mg, 0.16 mmol) in DMF (2 ml) was added DMF.DMA (100 μl, 0.75 mmol) and pyrrolidine (100 μl, 0.75 mmol) at 130° C. in one portion. The suspension was stirred for 2 h at 130° C. then cooled to room temperature and concentrated at reduced pressure. The residue was dissolved in 1:1 THF/MeOH (4 ml) and Raney Nickel (0.7 ml, 50% w/v in H2O) and hydrazine (0.7 ml, 1M solution in THF) were added. The reaction was stirred at room temperature for 3 hours then filtered over celite and concentrated at reduced pressure. The residue was purified by FCC (DCM/MeOH/NH3 with gradient, 98:2:1 to 95:5:1) to give the title compound (43 mg, 37%) as light brown oil.

Workup

  1. customat 130° C.
  2. temperaturethen cooled to room temperature
  3. concentrationconcentrated at reduced pressure
  4. dissolutionThe residue was dissolved in 1:1 THF/MeOH (4 ml) and Raney Nickel (0.7 ml, 50% w/v in H2O) and hydrazine (0.7 ml, 1M solution in THF)
  5. additionwere added
  6. stirringThe reaction was stirred at room temperature for 3 hours
  7. filtrationthen filtered over celite
  8. concentrationconcentrated at reduced pressure
  9. customThe residue was purified by FCC (DCM/MeOH/NH3 with gradient, 98:2:1 to 95:5:1)

Sources & evidence

ORD record
ord-74a7bf6156cb4761a3d94591f010b18c
Source dataset
uspto-grants-2014_04
Patent number
US08691804B2

Reaction notes

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