Pyridine → 1-Ethyl-3-{3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-urea

HRID 1506036ノート

反応式

HRID 1506036 の反応式
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([NH2:25])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1C=CC=CC=1.[CH2:34]([N:36]=[C:37]=[O:38])[CH3:35].C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO.O>[CH2:34]([NH:36][C:37]([NH:25][C:22]1[N:23]=[CH:24][C:19]2[NH:18][C:17]3[N:26]=[CH:27][C:14]([C:11]4[CH:12]=[CH:13][C:8]([CH2:7][N:1]5[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]5)=[CH:9][CH:10]=4)=[CH:15][C:16]=3[C:20]=2[CH:21]=1)=[O:38])[CH3:35]

参加物

8

反応物 4

HCID 1049PyridineHCID 8022Ethyl isocyanateHCID 516892Sodium BicarbonateHCID 58266504HCID 58266504、化合物

生成物 1

HCID 672012941-Ethyl-3-{3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-urea収率 31%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

A suspension of 3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-6-amine (91.6 mg, 0.256 mmol) in DCM (9.1 mL) was treated with pyridine (22.8 μL, 0.282 mmol) and ethylisocyanate (33.2 μL, 0.423 mmol) and then the reaction mixture was heated under reflux for 5 h. The cooled reaction mixture was treated with saturated sodium bicarbonate and diluted with 20% MeOH in DCM and water. The layers were separated, the aqueous phase extracted into 20% MeOH in DCM, and the combined organic phases were dried over sodium sulfate and concentrated in vacuo. The resultant residue was purified by preparative HPLC (0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min) to afford the title compound as a yellow solid (34 mg, 31%). 1H NMR (DMSO-D6, 400 MHz): 9.66 (t, J=5.4 Hz, 1H), 9.19 (s, 1H), 8.96 (d, J=2.1 Hz, 1H), 8.91 (d, J=2.1 Hz, 1H), 7.80 (d, J=8.1 Hz, 2H), 7.45 (d, J=8.1 Hz, 2H), 7.20 (s, 1H), 3.53-3.44 (m, 4H), 2.36 (m, 4H), 1.58-1.46 (m, 4H), 1.41 (m, 2H), 1.31-1.21 (m, 3H). LCMS (Method D): RT=8.06 min, M+H+=429.

後処理

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 5 h
  3. customThe cooled reaction mixture
  4. customThe layers were separated
  5. extractionthe aqueous phase extracted into 20% MeOH in DCM
  6. dry with materialthe combined organic phases were dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was purified by preparative HPLC (0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min)

出典と根拠

ORDレコード
ord-af3d3afa70b847d8a7945c43badd462e
出典データセット
uspto-grants-2015_12
特許番号
US09216980B2

反応ノート

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