Water → 3-(Benzyloxy)-N-(4-methylthiazol-2-yl)-5-(pyridin-3-yl)pyridin-2-amine dihydrochloride

HRID 1426118Notes

Reaction equation

HRID 1426118 reaction equation
[ClH:1].[CH2:2]([O:9][C:10]1[C:11]([NH:17][C:18]2[S:19][CH:20]=[C:21]([CH3:23])[N:22]=2)=[N:12][CH:13]=[C:14](Br)[CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[N:24]1[CH:29]=[CH:28][CH:27]=[C:26](B(O)O)[CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[ClH:1].[ClH:1].[CH2:2]([O:9][C:10]1[C:11]([NH:17][C:18]2[S:19][CH:20]=[C:21]([CH3:23])[N:22]=2)=[N:12][CH:13]=[C:14]([C:26]2[CH:25]=[N:24][CH:29]=[CH:28][CH:27]=2)[CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 160614653-(benzyloxy)-5-bromo-N-(4-methylthiazol-2-yl)pyridin-2-amine hydrochloride

Product 1

HCID 866396683-(Benzyloxy)-N-(4-methylthiazol-2-yl)-5-(pyridin-3-yl)pyridin-2-amine dihydrochloride

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

3-(Benzyloxy)-5-bromo-N-(4-methylthiazol-2-yl)pyridin-2-amine (prepared according to Example 1; 0.125 g, 0.332 mmol), pyridin-3-ylboronic acid (0.0490 g, 0.399 mmol), bis(triphenylphosphine)palladium(II) chloride (0.00700 g, 0.00997 mmol), and sodium carbonate (0.106 g, 0.997 mmol) were combined in DME (10 mL), and water (5 mL) and heated overnight at 80° C. The reaction mixture was cooled and partitioned between dichloromethane and water. The layers were separated, and the organic layer was dried, filtered, and concentrated. The residue was purified by silica gel chromatography to afford the title compound as the free base. The free base was dissolved in dichloromethane and 2M HCl in ether was added. The mixture was concentrated to afford 3-(benzyloxy)-N-(4-methylthiazol-2-yl)-5-(pyridin-3-yl)pyridin-2-amine dihydrochloride (0.109 g, 87.6% yield). 1H NMR (DMSO-d6) δ 9.27 (m, 1H), 8.81 (d, 1H), 8.75 (d, 1H), 8.48 (d, 1H), 8.08 (m, 1H), 7.97 (m, 1H), 7.66 (d, 2H), 7.43 (m, 2H), 7.37 (m, 1H), 6.82 (s, 1H), 5.45 (s, 2H), 2.31 (s, 3H). Mass spectrum (apci) m/z=375.1 (M+H-2HCl).

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between dichloromethane and water
  3. customThe layers were separated
  4. customthe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-b25edb966612475084fe8f81df0909bf
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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