Hydrochloric Acid → 1-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-cyclopentanecarboxylic acid

HRID 2110748Notes

Reaction equation

HRID 2110748 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]1([C:29]2[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][CH2:26][CH2:25]1)([OH:23])=[O:22].C([O-])([O-])=O.[Cs+].[Cs+].Cl>COCCOC.O.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>[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:31]2[CH:30]=[C:29]([C:24]3([C:21]([OH:23])=[O:22])[CH2:28][CH2:27][CH2:26][CH2:25]3)[CH:34]=[CH:33][CH:32]=2)[CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 576360046-Chloro-N-[2-(2,4-dichlorophenyl)ethyl]-2-methoxy-4-pyrimidinamineHCID 690700543-(1-Carboxy-cyclopentyl)-phenylboronic acid

Product 1

HCID 533165751-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-cyclopentanecarboxylic acid

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

Argon is bubbled through a mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine [330 mg, 0.99 mmol], 3-(1-carboxy-cyclopentyl)-phenylboronic acid [580 mg, 2.48 mmol] and Cs2CO3 (808 mg, 2.48 mmol) in ethylene glycol dimethyl ether (4 mL) and water (1 mL), for a period of 5 minutes. To this mixture is added tetrakis(triphenylphosphine)palladium (0) (116 mg, 0.1 mmol) and the reaction vessel is sealed and heated to 90° C. After stirring for 8 hours the mixture is diluted with water (30 mL) acidified to pH 1 with concentrated HCl and extracted thrice with EtOAc (30 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and concentrated to afford 1-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-cyclopentanecarboxylic acid as a solid that is treated with HCl in ethyl acetate. The material is then dissolved in acetone (5 mL) and heptane (15 mL) is added and allowed to stand at ambient temperature for 16 hours. The solvent is decanted from the crystals and dried under high vacuum to provide 1-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-cyclopentanecarboxylic acid hydrochloride [48 mg, 9%, Example 74] as a solid. LCMS RT=2.54 minutes, MS: 486 (M+H). IC50=0.5 nM

Workup

  1. customthe reaction vessel is sealed
  2. extractionextracted thrice with EtOAc (30 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-ad550d566711481dbc18c8f6f4d6352a
Source dataset
uspto-grants-2009_04
Patent number
US07517889B2

Reaction notes

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