Methanol → HCID 86709423, compound

HRID 882254Notes

Reaction equation

HRID 882254 reaction equation
[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]

Participants

7

Reactant 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

Product 1

HCID 86709423HCID 86709423, compoundYield 87%

Reagents, catalysts & solvents 2

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

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4878c2363614424eafab4a2d397d4be6
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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