Triethylamine → 1-(2-((2,5-Dichloropyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide

HRID 592376Notes

Reaction equation

HRID 592376 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1([C:12]([NH2:14])=[O:13])[CH2:11][CH2:10]1)#[CH:2].[Cl:15][C:16]1[N:21]=[C:20](Cl)[C:19]([Cl:23])=[CH:18][N:17]=1.CCN(CC)CC>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:15][C:16]1[N:21]=[C:20]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[C:9]2([C:12]([NH2:14])=[O:13])[CH2:11][CH2:10]2)[C:19]([Cl:23])=[CH:18][N:17]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 2372592,4,5-TrichloropyrimidineHCID 867122761-(2-Ethynylphenyl)cyclopropanecarboxamide

Product 1

HCID 867122941-(2-((2,5-Dichloropyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

PdCl2(PPh3)2 (16 mg, 0.023 mmol) was added to a stirred solution of 1-(2-ethynylphenyl)cyclopropanecarboxamide (K6) (0.420 g, 2.26 mmol), 2,4,5-trichloropyrimidine (0.338 mL, 2.94 mmol), Et3N (1.26 mL, 9.07 mmol) and copper(I) iodide (8.6 mg, 0.045 mmol) in 1,4-dioxane (4.5 mL). The resulting mixture was stirred at 60° C. for 2.5 hours under a nitrogen atmosphere before being diluted with petroleum benzine 40-60° C. (25 mL). The resultant precipitate was filtered, dried, washed with water (50 mL) and dried to give the title compound A13 as light coloured tan solid (0.570 g, 75%); 1H NMR (300 MHz, d6-DMSO) δ 9.01 (s, 1H), 7.72 (d, J=7.1 Hz, 1H), 7.41-7.57 (m, 3H), 6.97 (brs, 1H), 6.20 (brs, 1H), 1.53 (dq, J=4.0 Hz, 2H) 1.06 (dq, J=3.7 Hz, 2H). LCMS-B: rt 6.593 min; m/z 332 [M+H]+.

Workup

  1. filtrationThe resultant precipitate was filtered
  2. customdried
  3. washwashed with water (50 mL)
  4. customdried

Sources & evidence

ORD record
ord-a999d0892f80493cba8258bb57107222
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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