Triethylamine → HCID 53251116, compound

HRID 2407187Notes

Reaction equation

HRID 2407187 reaction equation
C(N(CC)CC)C.[C:8]([C:10]1[CH:11]=[CH:12][C:13]([CH3:16])=[N:14][CH:15]=1)#[CH:9].Br[C:18]1[C:26]2[NH:25][C:24]3[CH2:27][CH2:28][N:29]([CH3:31])[CH2:30][C:23]=3[C:22]=2[CH:21]=[CH:20][CH:19]=1>O1CCCC1.C(P([Pd]P(C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C)(C)C.[Cu]I>[CH3:31][N:29]1[CH2:28][CH2:27][C:24]2[NH:25][C:26]3[C:18]([C:9]#[C:8][C:10]4[CH:15]=[N:14][C:13]([CH3:16])=[CH:12][CH:11]=4)=[CH:19][CH:20]=[CH:21][C:22]=3[C:23]=2[CH2:30]1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 6381975-Ethynyl-2-methylpyridineHCID 63372946HCID 63372946, compound

Product 1

HCID 53251116HCID 53251116, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178454917HCID 178454917, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

Triethylamine (1.5 mL) was added to a mixture of bis(tri-t-butylphosphino)palladium (12.3 mg, 0.024 mmol; Aldrich), 5-ethynyl-2-methylpyridine (85 mg, 0.72 mmol; International Publication No. WO2005090333), CuI (4.6 mg, 0.024 mmol; Aldrich) and the product of Example 1A (128 mg, 0.48 mmol) in anhydrous tetrahydrofuran (1.5 mL). The mixture was purged with a nitrogen stream for 2 minutes, then stirred under nitrogen at 75° C. for 2 hours and then at 35° C. for 18 hours in a sealed tube. The mixture was filtered through a glass microfiber frit, rinsed with CH3OH (3 mL) and purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 50-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]. Fractions containing the product were concentrated under vacuum and the residue was further purified by flash chromatography (silica gel, eluted with CHCl3—CH3OH-14.8 M aqueous NH4OH (90:10:1)) to provide the title compound: 1H NMR (400 MHz, methanol-d4) δ ppm 2.55 (s, 3H), 2.56 (s, 3H), 2.89 (t, J=5.8 Hz, 2H), 2.98 (t, J=5.5 Hz, 2H), 3.69 (s, 2H), 6.97-7.04 (m, 1H), 7.25 (dd, J=7.3, 0.9 Hz, 1H), 7.33 (d, J=7.9 Hz, 1H), 7.41 (dd, J=7.8, 1.1 Hz, 1H), 7.94 (dd, J=7.9, 2.1 Hz, 1H), 8.68 (d, J=1.8 Hz, 1H); MS (DCI) m/z 302 (M+H)+.

Workup

  1. customThe mixture was purged with a nitrogen stream for 2 minutes
  2. waitat 35° C. for 18 hours in a sealed tube
  3. filtrationThe mixture was filtered through a glass microfiber frit
  4. washrinsed with CH3OH (3 mL)
  5. custompurified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 50-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]
  6. additionFractions containing the product
  7. concentrationwere concentrated under vacuum
  8. customthe residue was further purified by flash chromatography (silica gel, eluted with CHCl3—CH3OH-14.8 M aqueous NH4OH (90:10:1))

Sources & evidence

ORD record
ord-d652e301fbaf44389b250d2c7b1b8178
Source dataset
uspto-grants-2014_08
Patent number
US08809532B2

Reaction notes

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