(Bromoethynyl)benzene → (4-Methyl-pyridin-2-yl)-[6-(2-phenylethynyl-oxazol-5-yl)-pyridin-2-yl]-amine

HRID 1854617Notes

Reaction equation

HRID 1854617 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[O:19][CH:18]=[N:17][CH:16]=3)[N:10]=2)[CH:3]=1.Br[C:21]#[C:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1C=CC(P(C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC=2)C2C=CC=CC=2)=CC=1.O(C(C)(C)C)[Li]>O1CCOCC1.C1CC=CCCC=C1.C1CC=CCCC=C1.[Ni].O>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[O:19][C:18]([C:21]#[C:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[N:17][CH:16]=3)[N:10]=2)[CH:3]=1

Participants

8

Reactant 4

HCID 136737(Bromoethynyl)benzene2×HCID 4983791,2-Bis(diphenylphosphino)benzene2×HCID 53311228(4-Methyl-pyridin-2-yl)-(6-oxazol-5-yl-pyridin-2-yl)-amineHCID 178506942HCID 178506942, compound

Product 1

HCID 53312247(4-Methyl-pyridin-2-yl)-[6-(2-phenylethynyl-oxazol-5-yl)-pyridin-2-yl]-amineYield 13%

Reagents, catalysts & solvents 3

HCID 6433264Bis(1,5-cyclooctadiene)nickelCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

A sealed tube with a teflon screw cap was charged with a mixture of (4-methyl-pyridin-2-yl)-(6-oxazol-5-yl-pyridin-2-yl)-amine (200 mg, 0.793 mmol), bromoethynylbenzene (172 mg, 0.951 mmol) Ni(cod)2 (11 mg, 0.040 mmol), dppbz (18 mg, 0.040 mmol) and LiOtBu (127 mg, 1.59 mmol) in dry dioxane (5 ml) and heated to 100° C. for 2 h. Further bromoethynylbenzene (172 mg), Ni(cod)2 (11 mg), dppbz (18 mg) LiOtBu (127 mg, 1.59 mmol) and dry dioxane (2 ml) were added and heating continued for 36 h. The cooled mixture was treated with water and extracted with DCM. The combined organics were dried over MgSO4, filtered and evaporated under reduced pressure before purification by column chromatography on SiO2 eluting with 30% EtOAc in cyclohexane to afford the title compound as an off-white solid (35 mg, 13%). 1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 8.11 (d, J=5.1 Hz, 1H), 7.87 (s, J=26.8 Hz, 1H), 7.80-7.69 (m, 5H), 7.60-7.49 (m, 3H), 7.33 (d, J=7.2 Hz, 1H), 6.77 (d, J=5.1 Hz, 1H), 2.33 (s, 3H). (ESI+) m/z 353 (M+H)+. Retention time=3.24 mins (method 1).

Workup

  1. temperatureheating
  2. extractionextracted with DCM
  3. dry with materialThe combined organics were dried over MgSO4
  4. filtrationfiltered
  5. customevaporated under reduced pressure before purification by column chromatography on SiO2 eluting with 30% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-cec2e910d1064555adeea3f514b21649
Source dataset
uspto-grants-2015_02
Patent number
US08962665B2

Reaction notes

Loading…