Triethylamine → HCID 58654401, compound

HRID 1170531Notes

Reaction equation

HRID 1170531 reaction equation
[N:1]1([C:6]2[N:11]=[C:10]([CH:12]3[CH:16]([C:17]([OH:19])=O)[CH2:15][CH2:14][N:13]3[CH3:20])[CH:9]=[C:8]([CH3:21])[N:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O:46]1[C:51]2[CH:52]=[CH:53][C:54]([CH2:56][CH2:57][NH2:58])=[CH:55][C:50]=2[O:49][CH2:48][CH2:47]1.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[O:46]1[C:51]2[CH:52]=[CH:53][C:54]([CH2:56][CH2:57][NH:58][C:17]([CH:16]3[CH2:15][CH2:14][N:13]([CH3:20])[CH:12]3[C:10]3[CH:9]=[C:8]([CH3:21])[N:7]=[C:6]([N:1]4[CH:5]=[CH:4][N:3]=[CH:2]4)[N:11]=3)=[O:19])=[CH:55][C:50]=2[O:49][CH2:48][CH2:47]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 37470272-(2,3-Dihydro-1,4-benzodioxin-6-yl)ethan-1-amineHCID 58654390HCID 58654390, compound

Product 1

HCID 58654401HCID 58654401, compoundYield 7.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(2-Imidazol-1-yl-6-methyl-pyrimidin-4-yl)-1-methyl-pyrrolidine-3-carboxylic acid (27.0 mg, 0.094 mmol) was dissolved in DMF (1 mL). Next, the HBTU (54.0 mg, 0.141 mmol) was added. The reaction was stirred at room temperature for 30 minutes prior to addition of 2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-ethylamine (17.0 mg, 0.094 mmol) and the triethylamine (50 μL). The reaction was stirred at rt for 12 h then heated to 60° C. for 16 h. After this period, the reaction mixture was transferred to a separatory funnel with ethyl acetate (20 mL). The organic layer was washed with saturated NaHCO3 (aq) (30 mL) and H2O (30 mL), respectively. The aqueous layers were back extracted with ethyl acetate and all of the organic portions were combined, dried over Na2SO4 and concentrated under vacuum. The material was purified by Flash Chromatography (10 g, 0-10% methanol/DCM gradient) to afford 3.3 mg of 2-(2-imidazol-1-yl-6-methyl-pyrimidin-4-yl)-1-methyl-pyrrolidine-3-carboxylic acid [2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-ethyl]-amide. Product isolated as a mixture of diasteromers; [M+H]+ 449.84.

Workup

  1. stirringThe reaction was stirred at rt for 12 h
  2. temperaturethen heated to 60° C. for 16 h
  3. waitAfter this period
  4. washThe organic layer was washed with saturated NaHCO3 (aq) (30 mL) and H2O (30 mL)
  5. extractionThe aqueous layers were back extracted with ethyl acetate
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under vacuum
  8. customThe material was purified by Flash Chromatography (10 g, 0-10% methanol/DCM gradient)

Sources & evidence

ORD record
ord-f70e1d57edec4a628f16d2e509958808
Source dataset
uspto-grants-2010_11
Patent number
US07825256B2

Reaction notes

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