Cesium carbonate → 2-chloro-5-methyl-N-(pyridin-3-yl)pyrimidin-4-amine

HRID 491229

Reaction equation

HRID 491229 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[NH2:8][C:9]1[C:14]([CH3:15])=[CH:13][N:12]=[C:11]([Cl:16])[N:10]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Cl:16][C:11]1[N:10]=[C:9]([NH:8][C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)[C:14]([CH3:15])=[CH:13][N:12]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 122863-BromopyridineHCID 43021752-Chloro-5-methylpyrimidin-4-amine

Product 1

HCID 575165052-chloro-5-methyl-N-(pyridin-3-yl)pyrimidin-4-amineYield 57.1%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3-bromopyridine (379 mg, 2.4 mmol), 4-amino-2-chloro-5-methylpyrimidine (287 mg, 2.0 mmol), Pd2(dba)3 (18 mg, 0.02 mmol), xantphos (23 mg, 0.04 mmol) and cesium carbonate (975 mg, 3.0 mmol) in dioxane (15 mL) was heated under refluxed for 1 h under argon. The solvent was removed and the residue on purification by HPLC gave an intermediate, 2-chloro-5-methyl-N-(pyridin-3-yl)pyrimidin-4-amine as yellow solid (252 mg, 57%). For second Buckwald, a mixture of 2-chloro-5-methyl-N-(pyridin-3-yl)pyrimidin-4-amine (80 mg, 0.36 mmol), 4-(2-(pyrrolidin-1-yl)ethoxy)benzenamine (74 mg, 0.34 mmol), Pd2(dba)3 (3.2 mg, 0.003 mmol), xantphos (4.2 mg, 0.007 mmol) and cesium carbonate (234 mg, 0.72 mmol) in dioxane (5 mL) was heated under refluxed for 1 h under argon. The crude reaction mixture on purification using HPLC gave the title compound as light brown solid (28 mg, 20%).

Workup

  1. temperaturewas heated
  2. temperatureunder refluxed for 1 h under argon
  3. customThe solvent was removed
  4. customthe residue on purification by HPLC

Sources & evidence

ORD record
ord-791f3c64b07a45f48d9b42c795804a38
Source dataset
uspto-grants-2009_05
Patent number
US07528143B2

Linked notes

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