Epichlorohydrin → HCID 11452972, compound

HRID 2220507Notes

Reaction equation

HRID 2220507 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[I:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:18]3[CH2:19][N:20]([C:23](=[O:25])[CH3:24])[CH2:21][CH2:22][C:17]=3[NH:16][N:15]=2)=[CH:10][CH:9]=1.[CH2:26]([CH:28]1[O:30][CH2:29]1)Cl>CN(C=O)C>[I:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[C:18]3[CH2:19][N:20]([C:23](=[O:25])[CH3:24])[CH2:21][CH2:22][C:17]=3[N:16]([CH2:26][CH:28]3[CH2:29][O:30]3)[N:15]=2)=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 7835EpichlorohydrinHCID 10796Cesium carbonateHCID 11164488HCID 11164488, compound

Product 1

HCID 11452972HCID 11452972, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Cs2CO3 (1.30 g, 4.01 mmol) was added to a solution of 1-[3-(4-iodo-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (1.34 g, 3.65 mmol) and epichlorohydrin (2.85 mL, 36.4 mmol) in DMF (10.0 mL). The mixture was stirred for 17 h then partitioned between EtOAc (400 mL) and saturated NaHCO3 (150 mL). The NaHCO3 layer was extracted with EtOAc (2×150 mL). The combined extracts were washed with H2O (2×150 mL), brine (150 mL), dried over Na2SO4 and concentrated. The residue was purified by column chromatography (silica, 10-25% acetone/CH2Cl2) to give 890 mg (58%) of the title compound. HPLC, tR=5.53 min. (Reverse phase conditions: HP 1100 LCMS, Phenomenex luna 2.1×150 mm column, 60% MeOH/H2O (0.5% AcOH) to 90% MeOH/H2O (0.5% AcOH), held at initial conditions for 2 min then ramped to final conditions over 5 min.) MS (electrospray), m/z calculated for C17H18IN3O2 Na [M+Na]+ 445.04, found 445.95. 1H NMR (CDCl3, 500 MHz, a mixture of amide rotamers): 7.76 (d, J=8.3 Hz, 2H), 7.75 (d, J=8.3 Hz, 2H), 7.42 (d, J=8.2 Hz, 2H), 7.35 (d, J=8.2 Hz, 2H), 4.80 and 4.73 (A and B of AB quartet, Jab=15.6 Hz, 2H), 4.60 (s, 2H), 4.84 (dd, J=15.1, 2.1 Hz, 1H), 4.42 (dd, J=15.0, 2.1 Hz, 1H), 4.11 (t, J=5.0, Hz, 1H), 4.08 (t, J=5.0 Hz, 1H), 3.98-3.87 (m, 2H), 3.74 (m, 2H), 3.34 (m, 2H), 2.87-2.72 (m, 6H), 2.52 (dd, J=4.6, 2.6 Hz, 1H), 2.48 (dd, J=4.5, 2.6, 1H), 2.20 (s, 3H), 2.14 (s, 3H).

Workup

  1. customthen partitioned between EtOAc (400 mL) and saturated NaHCO3 (150 mL)
  2. extractionThe NaHCO3 layer was extracted with EtOAc (2×150 mL)
  3. washThe combined extracts were washed with H2O (2×150 mL), brine (150 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (silica, 10-25% acetone/CH2Cl2)

Sources & evidence

ORD record
ord-285e87b56fff4f78a23d3f9f55d388aa
Source dataset
uspto-grants-2008_08
Patent number
US07417046B2

Reaction notes

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