Ethanolamine → 6-(2,4-Dichloro-phenyl)-5-methylaminomethyl-2-phenyl-pyrimidin-4-ylamine

HRID 983876Notes

Reaction equation

HRID 983876 reaction equation
B1C2CCC[CH:2]1CCC2.[NH2:10][C:11]1[C:16]([C:17]#[N:18])=[C:15]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=2[Cl:26])[N:14]=[C:13]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:12]=1.CI.C(CN)O>CCCCCC.C1COCC1>[Cl:26][C:20]1[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:19]=1[C:15]1[N:14]=[C:13]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[N:12]=[C:11]([NH2:10])[C:16]=1[CH2:17][NH:18][CH3:2]

Participants

7

Reactant 4

HCID 700EthanolamineHCID 6328Methyl iodideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 155282984-Amino-6-(2,4-dichloro-phenyl)-2-phenyl-pyrimidine-5-carbonitrile

Product 1

HCID 101261346-(2,4-Dichloro-phenyl)-5-methylaminomethyl-2-phenyl-pyrimidin-4-ylamine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

Under an atmosphere of argon, 9-BBN (0.348 ml of a 0.5molar solution in hexane, 0.174 mmol) was added to a solution of 4-amino-6-(2,4-dichloro-phenyl)-2-phenyl-pyrimidine-5-carbonitrile (60 mg, 0.174 mmol) in THF (1 ml) and stirred for 2.5 h at r.t. Potassium-tert-butylate (20 mg, 0.174 mmol) was added, followed by a drop of Methyl iodide after 10 min. The mixture was stirred overnight, then ethanolamine (11 mg, 0.174 mmol) was added and the mixture was heated to 50° C. for 3 h. After cooling, the mixture was filtered, and the filtrate was evaporated. Purification of the re-dissolved (DMF, 1 ml) residue by automated, preparative HPLC (YMC CombiPrep C18 column 50×20 mm, solvent gradient 5-95% CH3CN in 0.1% TFA(aq) over 6.0 min, λ=230 nm, flow rate 40 ml/min) gave the title compound, MS: m/e=358.9 (M+H+), (12 mg, 19%) as a foam.

Workup

  1. stirringThe mixture was stirred overnight
  2. temperaturethe mixture was heated to 50° C. for 3 h
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered
  5. customthe filtrate was evaporated
  6. customPurification of the
  7. dissolutionre-dissolved (DMF, 1 ml) residue by automated, preparative HPLC (YMC CombiPrep C18 column 50×20 mm, solvent gradient 5-95% CH3CN in 0.1% TFA(aq) over 6.0 min, λ=230 nm, flow rate 40 ml/min)

Sources & evidence

ORD record
ord-f99b2437b03b4a6f952e4cfafdfec48d
Source dataset
uspto-grants-2005_03
Patent number
US06867205B2

Reaction notes

Loading…