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

HRID 1854617ノート

反応式

HRID 1854617 の反応式
[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

参加物

8

反応物 4

HCID 136737(Bromoethynyl)benzene2 回HCID 4983791,2-Bis(diphenylphosphino)benzene2 回HCID 53311228(4-Methyl-pyridin-2-yl)-(6-oxazol-5-yl-pyridin-2-yl)-amineHCID 178506942HCID 178506942、化合物

生成物 1

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

試薬・触媒・溶媒 3

HCID 6433264Bis(1,5-cyclooctadiene)nickel触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-cec2e910d1064555adeea3f514b21649
出典データセット
uspto-grants-2015_02
特許番号
US08962665B2

反応ノート

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