Sodium Bicarbonate → N-(4-methylthiazol-2-yl)-3-phenoxy-5-(pyridin-3-yl)pyridin-2-amine

HRID 1806013Notes

Reaction equation

HRID 1806013 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)=[N:6][CH:7]=1.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=1.C(=O)(O)[O-].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[CH3:14][C:12]1[N:13]=[C:9]([NH:8][C:5]2[C:4]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:3][C:2]([C:24]3[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=3)=[CH:7][N:6]=2)[S:10][CH:11]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 27343783-Pyridinylboronic acidHCID 247655435-Bromo-N-(4-methylthiazol-2-yl)-3-phenoxypyridin-2-amine

Product 1

HCID 24765544N-(4-methylthiazol-2-yl)-3-phenoxy-5-(pyridin-3-yl)pyridin-2-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

5-Bromo-N-(4-methylthiazol-2-yl)-3-phenoxypyridin-2-amine (0.070 g, 0.1932 mmol), pyridin-3-ylboronic acid (0.02850 g, 0.2319 mmol), Pd(PPh3)4 (0.02233 g, 0.01932 mmol), DME (10 mL), and 2M sodium bicarbonate (2 mL) were combined, heated to 80° C. and stirred overnight. The reaction mixture was cooled and partitioned between CH2Cl2 and water. The organic layer was dried, filtered, and concentrated. The residue was purified by silica gel chromatography (30-40% EtOAc in hexane) to give N-(4-methylthiazol-2-yl)-3-phenoxy-5-(pyridin-3-yl)pyridin-2-amine. N-(4-methylthiazol-2-yl)-3-phenoxy-5-(pyridin-3-yl)pyridin-2-amine was dissolved in CH2Cl2 and 2M HCl in ether was added to give N-(4-methylthiazol-2-yl)-3-phenoxy-5-(pyridin-3-yl)pyridin-2-amine dihydrochloride (0.050 g, 59.71% yield). 1H NMR (d6-DMSO) δ 9.19 (d, 1H), 8.78 (dd, 1H), 8.70 (m, 2H), 7.93 (m, 2H), 7.42 (t, 2H), 7.18 (t, 1H), 7.12 (d, 2H), 6.74 (s, 1H), 2.28 (s, 3H); Mass spectrum (apci) m/z=361.2 (M+H-2HCl).

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between CH2Cl2 and water
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (30-40% EtOAc in hexane)

Sources & evidence

ORD record
ord-137ec1c8e4a14cc7a28f347223860e23
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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