Sodium Carbonate → N-(4-methylthiazol-2-yl)-3-phenoxy-5-phenylpyridin-2-amine hydrochloride

HRID 1806010Notes

Reaction equation

HRID 1806010 reaction equation
[Cl:1][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.[C:22]1(B(O)O)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[ClH:1].[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:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:7][N:6]=2)[S:10][CH:11]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic Acid2×HCID 247655385-chloro-N-(4-methylthiazol-2-yl)-3-phenoxypyridin-2-amine

Product 1

HCID 24765541N-(4-methylthiazol-2-yl)-3-phenoxy-5-phenylpyridin-2-amine hydrochlorideYield 7.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

5-Chloro-N-(4-methylthiazol-2-yl)-3-phenoxypyridin-2-amine (0.150 g, 0.472 mmol), phenylboronic acid (0.0691 g, 0.566 mmol), Pd(PPh3)4 (0.0545 g, 0.0472 mmol), in DME (10 mL), and 2M Na2CO3 (5 mL) were placed in a round bottom flask, heated to 80° C. and stirred overnight. An extra equivalent of Pd(PPh3)4 (0.0545 g, 0.0472 mmol), and phenylboronic acid (0.0691 g, 0.566 mmol) were added and the reaction mixture was heated for 2 weeks. The reaction mixture was cooled to room temperature and partitioned between CH2Cl2 and water. The organic layer was dried, filtered, and concentrated. The residue was purified by silica gel chromatography and then by reverse phase chromatography to give the title compound (0.0134 g, 7.17% yield) after salt formation. 1H NMR (d6-DMSO) δ 8.53 (d, 1H), 7.65 (m, 3H), 7.45 (m, 4H), 7.37 (m, 1H), 7.21 (t, 1H), 7.16 (d, 2H), 6.78 (s, 1H), 2.29 (s, 3H); Mass spectrum (apci) m/z=360.3 (M+H—HCl).

Workup

  1. temperaturethe reaction mixture was heated for 2 weeks
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompartitioned between CH2Cl2 and water
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f5ed03ba74ca4a05bcd86e1c55851265
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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