2-Piperidone → 1-{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-piperidin-2-one

HRID 1773900ノート

反応式

HRID 1773900 の反応式
[Na].[C:2]1(=[O:8])[NH:7][CH2:6][CH2:5][CH2:4][CH2:3]1.Br[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:25]=[C:24]3[N:18]([CH2:19][CH2:20][C:21]4[CH:37]=[CH:36][CH:35]=[CH:34][C:22]=4[CH:23]3[O:26][CH:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)[C:17]=2[CH3:38])=[CH:12][CH:11]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1(C)C=CC=CC=1.CO>[CH3:38][C:17]1[N:18]2[C:24]([CH:23]([O:26][CH:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)[C:22]3[CH:34]=[CH:35][CH:36]=[CH:37][C:21]=3[CH2:20][CH2:19]2)=[N:25][C:16]=1[C:13]1[CH:14]=[CH:15][C:10]([N:7]2[CH2:6][CH2:5][CH2:4][CH2:3][C:2]2=[O:8])=[CH:11][CH:12]=1

参加物

8

反応物 4

HCID 126652-PiperidoneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 5360545SodiumHCID 726953822-(4-bromophenyl)-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

生成物 1

HCID 867039761-{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-piperidin-2-one

試薬・触媒・溶媒 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 887Methanol溶媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

In a screw-capped vial are added MeOH (3.5 mL) and sodium metal (2 mg). After 10 min, valerolactam (16 mg, 0.16 mmole) is added. The solvent is removed under reduced pressure. To the residual solid are added 2-(4-bromophenyl)-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 122A) (50 mg, 0.107 mmole), Pd(dba)2 (4.9 mg, 5.3 μmole), Xantphos (6.2 mg, 10.6 μmole), toluene (0.7 mL). The flask is evacuated and filled with argon and the reaction mixture is heated at 110° C. overnight. Water is added and pH adjusted to 10 with a few drops of 1N NaOH. The aqueous phase is extracted three times with CH2Cl2. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) with a gradient from (100:0:0) to (96.5:3.5:0.35) to give 1-{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-piperidin-2-one.

後処理

  1. customThe solvent is removed under reduced pressure
  2. customThe flask is evacuated
  3. additionfilled with argon
  4. additionWater is added
  5. extractionThe aqueous phase is extracted three times with CH2Cl2
  6. dry with materialThe organic phase is dried over magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent is removed under reduced pressure
  9. customThe residue is purified by silica gel chromatography

出典と根拠

ORDレコード
ord-06f33a0cf9ee4fe7aa7a4ae8e370a6fd
出典データセット
uspto-grants-2016_02
特許番号
US09255101B2

反応ノート

読み込み中…