HCID 118383913, compound → HCID 118383914, compound

HRID 1771973Notes

Reaction equation

HRID 1771973 reaction equation
O1C=N[C:3]([C:6]([NH:9][C:10]([C:12]2[CH:13]=[C:14]([C:18]3[CH:19]=[C:20]4[C:29]([C:30]([NH:32][CH3:33])=[O:31])=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=5)[O:27][C:21]4=[N:22][C:23]=3/[CH:24]=[CH:25]/[CH3:26])[CH:15]=[CH:16][CH:17]=2)=[O:11])([CH3:8])[CH3:7])=[N:2]1>CO.[Pd]>[C:3]([C:6]([NH:9][C:10]([C:12]1[CH:13]=[C:14]([C:18]2[CH:19]=[C:20]3[C:29]([C:30]([NH:32][CH3:33])=[O:31])=[C:28]([C:34]4[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=4)[O:27][C:21]3=[N:22][C:23]=2[CH2:24][CH2:25][CH3:26])[CH:15]=[CH:16][CH:17]=1)=[O:11])([CH3:7])[CH3:8])#[N:2]

Participants

4

Reactant 1

HCID 118383913HCID 118383913, compound

Product 1

HCID 118383914HCID 118383914, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent

Procedure

Pd/C (9.0 mg, 8.5 μmol) was added to a stirring solution of (E)-5-(3-((2-(1,2,4-oxadiazol-3-yl)propan-2-yl)carbamoyl)phenyl)-2-(4-fluorophenyl)-N-methyl-6-(prop-1-en-1-yl)furo[2,3-b]pyridine-3-carboxamide (23 mg, 0.043 mmol) in MeOH (853 μl) at room temperature. The reaction mixture was placed in a Parr bomb and charged with 25 PSI of H2 (g) and the reaction mixture was allowed to stir for 4 hours. LCMS indicated no conversion. Pd/C (9.0 mg, 8.5 μmol) was added and the reaction mixture was placed in a Parr bomb and charged with 50 PSI of H2 (g) and the reaction mixture was allowed to stir for 16 hours. The reaction mixture was filtered and purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/CH3CN gradient, and concentrated to give 5-(3-((2-cyanopropan-2-yl)carbamoyl)phenyl)-2-(4-fluorophenyl)-N-methyl-6-propylfuro[2,3-b]pyridine-3-carboxamide (2.5 mg, 4.7 μmol, 11% yield) consistent by LCMS and NMR. 1H NMR (400 MHz, CDCl3) δ 8.01-7.95 (m, 2H), 7.94 (s, 1H), 7.82 (d, J=7.5 Hz, 1H), 7.70 (s, 1H), 7.56-7.45 (m, 2H), 7.22 (t, J=8.7 Hz, 2H), 6.58 (s, 1H), 6.09-6.01 (m, 1H), 2.99 (d, J=5.0 Hz, 3H), 2.74-2.67 (m, 2H), 1.86 (s, 6H), 1.71-1.65 (m, 2H), 0.85 (t, J=7.4 Hz, 3H). LC-MS retention time: 2.05 min; m/z (M+H)+: 499. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u C18 2.0×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% methanol/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% methanol/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. additioncharged with 25 PSI of H2 (g)
  2. additioncharged with 50 PSI of H2 (g)
  3. stirringto stir for 16 hours
  4. filtrationThe reaction mixture was filtered
  5. custompurified by preparative reverse phase HPLC on a C18 column
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5ef630ba368445d897b6da3e84480ba1
Source dataset
uspto-grants-2016_02
Patent number
US09249152B2

Reaction notes

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