Hydrochloric Acid → Pgd2-IN-1

HRID 1988568Notes

Reaction equation

HRID 1988568 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[Cl:20])[CH:3]=1.[C:21]([C:24]([C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1)([CH3:26])[CH3:25])([OH:23])=[O:22].O.Cl>C(#N)C.C(=O)([O-])[O-].[Na+].[Na+]>[Cl:20][C:14]1[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=1[CH2:12][CH2:11][NH:10][C:4]1[N:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([C:29]2[CH:28]=[C:27]([C:24]([CH3:26])([CH3:25])[C:21]([OH:23])=[O:22])[CH:32]=[CH:31][CH:30]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 442489972-(3-Boronophenyl)-2-methylpropanoic acidHCID 576360046-Chloro-N-[2-(2,4-dichlorophenyl)ethyl]-2-methoxy-4-pyrimidinamine

Product 1

HCID 11669780Pgd2-IN-1Yield 87.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
130 °C

Procedure

A solution of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine (0.51 mmol) and 3-(1-carboxy-1-methyl-ethyl)-phenyl boronic acid (0.61 mmol) in acetonitrile (2.5 mL) and aqueous sodium carbonate solution (0.4 M, 2.5 mL) is degassed with nitrogen for 5 minutes before addition of tetrakistriphenylphosphine palladium (0) (29.5 mg, 5 mol %). The reaction vessel is sealed and heated under microwave to 130° C. for 30 minutes. To the reaction mixture is added 2 mL of water, the pH is adjusted to about 7 using 2 N aqueous HCl and this mixture is extracted three times with ethyl acetate (30 mL). The combined extracts are washed with brine, dried over sodium sulfate and concentrated. The residue is subjected to silica gel chromatography to afford 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid as a solid (205 mg, 75%). LC/MS: RT=2.39 minutes, MS: 460 (M+H); 1H NMR [300 MHz, (CD3)2SO]: δ 12.38 (1H, s), 7.36-8.00 (7H, m), 6.58 (1H, s), 3.84 (3H, s), 3.58 (2H, m), 2.98 (2H, m), 1.54 (6H, s).

Workup

  1. customThe reaction vessel is sealed
  2. extractionthis mixture is extracted three times with ethyl acetate (30 mL)
  3. washThe combined extracts are washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-1d653521ba4844cbb1bbdc44b701d5bc
Source dataset
uspto-grants-2010_01
Patent number
US07642249B2

Reaction notes

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