Methanol → HCID 86709423, 화합물

HRID 882254노트

반응식

HRID 882254 반응식
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](Br)=[CH:11][CH:12]=2)[C@H:7]([NH2:15])[CH2:6][C@@H:5]1[CH3:16])(=[O:3])[CH3:2].CC1(C)C(C)(C)OB([C:25]2[CH:26]=[CH:27][C:28]([C:31]([O:33][CH3:34])=[O:32])=[N:29][CH:30]=2)O1.C(N(CC)CC)C.CO>COCCOC.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:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:25]3[CH:26]=[CH:27][C:28]([C:31]([O:33][CH3:34])=[O:32])=[N:29][CH:30]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:15])[CH2:6][C@@H:5]1[CH3:16])(=[O:3])[CH3:2]

참가 물질

7

반응물 4

HCID 887MethanolHCID 8471TriethylamineHCID 467386632-Methoxycarbonyl-5-pyridineboronic acid, pinacol esterHCID 67194540cis-1-Acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine

생성물 1

HCID 86709423HCID 86709423, 화합물수율 87%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 80711,2-Dimethoxyethane용매

실험 절차

In a separate vial, (2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine (for a preparation, see Intermediate 1) (50 mg, 0.156 mmol), methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate (49.4 mg, 0.188 mmol), PdCl2(dppf) (17.17 mg, 0.023 mmol) and triethylamine (0.065 mL, 0.469 mmol) were combined in DME (0.5 mL) and MeOH (1 mL) and the mixture heated under microwave irradiation to 110° C. for 45 mins. The two crude reaction mixtures were combined and concentrated in vacuo. The residue was purified by chromatography (100 g column, EtOAc/cyclohexane followed by 2M methanolic ammonia/DCM gradient). The appropriate fractions were combined, concentrated in vacuo and dried in a vacuum oven to give a residue. This residue was partitioned between sat. aq. sodium bicarbonate (100 mL) and DCM (3×100 mL). The organic layers were combined, dried by passing through a hydrophobic frit and concentrated in vacuo to give methyl 5-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)picolinate (555 mg, 1.64 mmol, 87% yield).

후처리

  1. customThe two crude reaction mixtures
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by chromatography (100 g column, EtOAc/cyclohexane followed by 2M methanolic ammonia/DCM gradient)
  4. concentrationconcentrated in vacuo
  5. customdried in a vacuum oven
  6. customto give a residue
  7. customThis residue was partitioned between sat. aq. sodium bicarbonate (100 mL) and DCM (3×100 mL)
  8. customdried
  9. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-4878c2363614424eafab4a2d397d4be6
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993554B2

반응 노트

불러오는 중…