Triethylamine → HCID 86670614, compound

HRID 2036781Notes

Reaction equation

HRID 2036781 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:3]=1.C[Si]([C:30]#[CH:31])(C)C.CCN(CC)CC>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:30]([C:2]1[N:11]=[C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:3]=1)#[CH:31]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 866706132-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine

Product 1

HCID 86670614HCID 86670614, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (1.0 g, 2.8 mmol) in DMF (10 mL) under nitrogen was added trimethylsilylacetylene (2.0 mL, 14 mmol), cupric iodide (0.11 g, 0.58 mmol) and Et3N (1.2 mL, 8.4 mmol). Upon completion of addition, the mixture was degassed with nitrogen for 15 min. Tetrakis(triphenylphosphine)palladium (0.20 g, 0.28 mmol) was then added and the resulting mixture was again degassed with nitrogen for 10 min. After this time, the reaction mixture was heated in a sealed tube to 120° C. where it stirred for 16 h. At the conclusion of this period, the reaction mixture was allowed to cool to room temperature. Once at the prescribed temperature, the reaction mixture was quenched by the addition of water. The resulting reaction mixture was extracted with ethyl acetate and the organic layer was washed successively with water and brine. The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting concentrate was dissolved in methanol and saturated with ammonia gas. The saturated solution was stirred for 2 h at 0° C. and then concentrated under reduced pressure to yield a residue. The residue was purified by flash column chromatography using ethyl acetate and petroleum ether to afford 2-ethynyl-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (650 mg). 1H NMR (400 MHz, CDCl3) δ (ppm): 8.15 (d, J=4.0 Hz, 1H), 7.86 (dd, J=8.4, 1.2 Hz, 1H), 7.69 (t, J=8.4 Hz, 1H), 7.56 (dt, J=3.6, 1.6 Hz, 1H), 7.49-7.42 (m, 5H), 7.26-7.23 (m, 1H), 7.13-7.08 (m, 2H), 6.94 (bs, 1H), 4.67 (d, J=10.0 Hz, 2H), 3.02 (s, 1H). LCMS Method O: retention time 1.35 min, [M+1]=337.0.

Workup

  1. additionUpon completion of addition
  2. customthe mixture was degassed with nitrogen for 15 min
  3. customthe resulting mixture was again degassed with nitrogen for 10 min
  4. temperatureto cool to room temperature
  5. customOnce at the prescribed temperature, the reaction mixture was quenched by the addition of water
  6. customThe resulting reaction mixture
  7. extractionwas extracted with ethyl acetate
  8. washthe organic layer was washed successively with water and brine
  9. dry with materialThe combined organic layers were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. concentrationThe resulting concentrate
  13. dissolutionwas dissolved in methanol and saturated with ammonia gas
  14. stirringThe saturated solution was stirred for 2 h at 0° C.
  15. concentrationconcentrated under reduced pressure
  16. customto yield a residue
  17. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-c6ff7e33231641e380631cca53863752
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

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