2-Vinylpyridine → HCID 86651951, compound

HRID 1615252Notes

Reaction equation

HRID 1615252 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=[O:12])=[CH:8][CH:9]=2)[N:4]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)[N:3]=1.[CH:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)=[CH2:20].CCN(C(C)C)C(C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C>[N:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1/[CH:19]=[CH:20]/[C:2]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=[O:12])=[CH:8][CH:9]=2)[N:4]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)[N:3]=1

Participants

7

Reactant 4

HCID 75212-VinylpyridineHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 86651950HCID 86651950, compound

Product 1

HCID 86651951HCID 86651951, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

In a scintillation vial a solution of 3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-6-carbaldehyde (24 mg, 0.0673 mmol), 2-vinylpyridine (9.4 uL, 0.0875 mmol), DIPEA (24 uL, 0.135 mmol) and DMF (1.0 mL) was purged with Ar for 20 min. Pd(OAc)2 (1.5 mg, 0.0067 mmol) and P(o-tolyl)3 (6.1 mg, 0.0202 mmol) were then added and the vial was capped and heated to 100° C. overnight. The solution was cooled to room temperature and extracted with EtOAc, washing with NH4Cl(sat.), H2O, and brine. The organic layer was dried over MgSO4, the solvent removed in vacuo, and the residue purified by column chromatography (silica gel, 96:4 CH2Cl2/MeOH) to give 17 mg, 77% of a yellow oil which was 70% pure by NMR. This crude material was used for the subsequent synthetic step. 1H NMR (400 MHz, CD3OD) δ 10.16 (s, 1H), 8.59 (s, 1H), 8.34 (s, 1H), 8.27 (d, J=8.4 Hz, 1H), 7.95-7.83 (m, 4H), 7.75 (m, 1H), 7.68 (d, J=16.0 Hz, 1H), 6.00 (d, J=9.6 Hz, 1H), 4.05-4.01 (m, 1H), 3.93-3.86 (m, 1H), 2.65-2.56 (m, 1H), 2.27-2.10 (m, 2H), 1.92-1.66 (m, 3H); MS ESI 334.1 [M+H]+, calcd for [C20H19N3O2+H]+ 334.16.

Workup

  1. customthe vial was capped
  2. temperatureThe solution was cooled to room temperature
  3. extractionextracted with EtOAc
  4. washwashing with NH4Cl(sat.), H2O, and brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. customthe solvent removed in vacuo
  7. customthe residue purified by column chromatography (silica gel, 96:4 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-260695c95a9c43b191c0f0501145e6dd
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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