5-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-oxazole → 6-(Oxazol-5-yl)-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1506059ノート

反応式

HRID 1506059 の反応式
Br[C:2]1[N:10]=[CH:9][C:8]2[NH:7][C:6]3[N:11]=[CH:12][C:13]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][N:22]5[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]5)=[CH:17][CH:16]=4)=[CH:14][C:5]=3[C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:36]2[O:40][CH:39]=[N:38][CH:37]=2)O1>C(=O)([O-])[O-].[Na+].[Na+].C(#N)C.C(Cl)Cl.CO>[O:40]1[C:36]([C:2]2[N:10]=[CH:9][C:8]3[NH:7][C:6]4[N:11]=[CH:12][C:13]([C:15]5[CH:16]=[CH:17][C:18]([CH2:21][N:22]6[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]6)=[CH:19][CH:20]=5)=[CH:14][C:5]=4[C:4]=3[CH:3]=2)=[CH:37][N:38]=[CH:39]1

参加物

7

反応物 2

HCID 534270915-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-oxazoleHCID 582663876-Bromo-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

生成物 1

HCID 582665796-(Oxazol-5-yl)-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole収率 29%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒HCID 10340Sodium Carbonate溶媒

反応条件

温度
130 °C

実験手順

A mixture of 6-bromo-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (150 mg, 0.36 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)oxazole (140 mg, 0.71 mmol), 1,1′-[bis(diphenylphosphino)-ferrocene]dichloropalladium(II) (29 mg, 0.004 mmol) in saturated aqueous sodium carbonate solution (0.5 mL) and acetonitrile (5 mL) was heated under microwave irradiation at 130° C. for 30 minutes. The cooled reaction mixture was diluted with DCM (20 mL) and methanol (2 mL) and washed with water (15 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by preparative HPLC [20-60% MeCN in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min] to afford the title compound as an off-white solid (42 mg, 29%). 1H NMR (DMSO-D6, 400 MHz): 12.42 (s, 1H), 9.12 (d, J=2.2 Hz, 1H), 8.96 (s, 1H), 8.94 (d, J=2.2 Hz, 1H), 8.67 (s, 1H), 8.52 (s, 1H), 7.78 (d, J=8.1 Hz, 2H), 7.66 (s, 1H), 7.44 (d, J=8.1 Hz, 2H), 3.50 (s, 2H), 2.37 (s, 4H), 1.51 (m, 4H), 1.40 (m, 2H). LCMS (Method D): RT=7.76 min, M+H+=410.

後処理

  1. customThe cooled reaction mixture
  2. washwashed with water (15 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by preparative HPLC [20-60% MeCN in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min]

出典と根拠

ORDレコード
ord-8c7e95ea016a463f9c7eac7f150558c1
出典データセット
uspto-grants-2015_12
特許番号
US09216980B2

反応ノート

読み込み中…