Water → 5-(4-chlorophenyl)-5-[3-(2,5-dimethylpyrrolidin-1-yl)-3-oxopropyl]-7-methyl-5H-imidazo[2,1-a]isoindole

HRID 46181

반응식

HRID 46181 반응식
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[C:12]1=[N:16][CH:17]=[CH:18][N:11]1[C:10]2([C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)[CH2:19][CH2:20][C:21]([N:23]1[CH:27]([CH3:28])[CH2:26][CH2:25][CH:24]1[CH3:29])=[O:22])(=O)=O.[CH3:39]B(O)O.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([C:10]2([CH2:19][CH2:20][C:21]([N:23]3[CH:27]([CH3:28])[CH2:26][CH2:25][CH:24]3[CH3:29])=[O:22])[C:9]3[C:13](=[CH:14][CH:15]=[C:7]([CH3:39])[CH:8]=3)[C:12]3=[N:16][CH:17]=[CH:18][N:11]23)=[CH:31][CH:32]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 139377Methylboronic AcidHCID 866572495-(4-chlorophenyl)-5-[3-(2,5-dimethylpyrrolidin-1-yl)-3-oxopropyl]-5H-imidazo[2,1-a]isoindol-7-yl trifluoromethanesulfonate

생성물 1

HCID 462062535-(4-chlorophenyl)-5-[3-(2,5-dimethylpyrrolidin-1-yl)-3-oxopropyl]-7-methyl-5H-imidazo[2,1-a]isoindole수율 41.9%

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

5-(4-chlorophenyl)-5-[3-(2,5-dimethylpyrrolidin-1-yl)-3-oxopropyl]-5H-imidazo[2,1-a]isoindol-7-yl trifluoromethanesulfonate (50 mg), methylboronic acid (8 mg), K2CO3 (37 mg), and PdCl2(dppf)-CH2Cl2 adduct (8 mg) were combined in 1,4-dioxane (400 μL):H2O (40.0 μL). The mixture was degassed (3× pump/N2) then heated to 100° C. After 3 h the mixture was cooled to room temperature and concentrated. The residue was taken up in DMF, filtered using a 0.45 μm PTFE syringe filter, then purified by preparative reversed-phase HPLC (21×100 mm Phenomenex Gemini (5-95% ACN/water containing 0.05% NH4OH over 20 min at 20 mL/min) to give a light grey solid (16 mg): 1H-NMR (400 MHz, CDCl3) δ 7.71 (d, J=7.79 Hz, 1 H), 7.27 (m, 3 H), 7.19 (m, 1 H), 7.12 (dd, J=3.66 and 5.04 Hz, 2 H), 7.03 (bs, 1 H), 6.93 (dd, J=1.19 and 7.88 Hz, 1 H), 3.89 (m, 1 H), 3.41 (m, 1 H), 3.20-2.75 (m, 2 H), 2.34 (d, J=2.74 Hz, 3 H), 1.97-1.63 (m, 2 H), 1.50 (m, 4 H), 1.17 (dd, J=6.32 and 8.43 Hz, 3 H), 0.86 (dd, J=6.50 and 27.1 Hz, 3 H); HRMS (M+H)+ calculated 434.1994. found 434.1993.

후처리

  1. customThe mixture was degassed (3× pump/N2)
  2. temperatureAfter 3 h the mixture was cooled to room temperature
  3. concentrationconcentrated
  4. filtrationfiltered
  5. filtrationfilter
  6. custompurified by preparative reversed-phase HPLC (21×100 mm Phenomenex Gemini (5-95% ACN/water containing 0.05% NH4OH over 20 min at 20 mL/min)

출처 및 근거

ORD 기록
ord-31d3012785c74737a5c0b02dfe260494
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541595B2

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