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 1773900노트

반응식

HRID 1773900 반응식
[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

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium촉매HCID 887Methanol용매HCID 1140Toluene용매

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온도
110 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-06f33a0cf9ee4fe7aa7a4ae8e370a6fd
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09255101B2

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