1-(Propan-2-yl)-1,4-diazepane → HCID 178489791, compound

HRID 1092159Notes

Reaction equation

HRID 1092159 reaction equation
[CH:1]([N:4]1[CH2:10][CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)([CH3:3])[CH3:2].Cl[C:12]1[N:13]=[CH:14][C:15]([C:18]([NH:20][C:21]2[NH:22][N:23]=[C:24]([CH2:26][CH2:27][C:28]3[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[C:30]([O:36][CH3:37])[CH:29]=3)[CH:25]=2)=[O:19])=[N:16][CH:17]=1>CS(C)=O.CO>[CH3:35][O:34][C:32]1[CH:33]=[C:28]([CH2:27][CH2:26][C:24]2[CH:25]=[C:21]([NH:20][C:18]([C:15]3[CH:14]=[N:13][C:12]([N:7]4[CH2:8][CH2:9][CH2:10][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]4)=[CH:17][N:16]=3)=[O:19])[NH:22][N:23]=2)[CH:29]=[C:30]([O:36][CH3:37])[CH:31]=1

Participants

5

Reactant 2

HCID 122365131-(Propan-2-yl)-1,4-diazepaneHCID 178489782HCID 178489782, compound

Product 1

HCID 178489791HCID 178489791, compoundYield 42.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

1-isopropyl-1,4-diazepane (228 mg, 1.60 mmol) was added to 5-chloro-N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]pyrazine-2-carboxamide (310 mg, 0.80 mmol) in DMSO (4.00 ml) at 25° C. The resulting solution was stirred at room temperature for 2 hours. The reaction was incomplete so the temperature was increased to 60° C. and the reaction mixture was stirred for a further 2 h. The reaction was still incomplete so the reaction mixture was stirred for a further 18 h at room temperature. The reaction mixture was diluted with MeOH (5 ml) and the crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 7M NH3/MeOH and fractions were evaporated to dryness to afford crude product as an orange dry film. The crude product was purified by preparative HPLC, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title compound (167 mg, 42%) as a pale yellow solid.

Workup

  1. temperaturewas increased to 60° C.
  2. stirringthe reaction mixture was stirred for a further 2 h
  3. stirringwas stirred for a further 18 h at room temperature
  4. customthe crude product was purified by ion exchange chromatography
  5. washThe desired product was eluted from the column
  6. customwere evaporated to dryness
  7. customto afford crude product as an orange dry film
  8. customThe crude product was purified by preparative HPLC
  9. additionFractions containing the desired compound
  10. customwere evaporated to dryness

Sources & evidence

ORD record
ord-f422e9c365e04e7fb198e8bd27559980
Source dataset
uspto-grants-2012_03
Patent number
US08129391B2

Reaction notes

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