Phenylboronic Acid → 1-{2-[4-(5-Chlorothiophen-2-yl)-5-phenylpyrimidin-2-ylamino]ethyl}-5,5-dimethylimidazolidine-2,4-dione

HRID 507586Notes

Reaction equation

HRID 507586 reaction equation
Br[C:2]1[C:3]([C:20]2[S:21][C:22]([Cl:25])=[CH:23][CH:24]=2)=[N:4][C:5]([NH:8][CH2:9][CH2:10][N:11]2[C:15]([CH3:17])([CH3:16])[C:14](=[O:18])[NH:13][C:12]2=[O:19])=[N:6][CH:7]=1.[C:26]1(B(O)O)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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:25][C:22]1[S:21][C:20]([C:3]2[C:2]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:7][N:6]=[C:5]([NH:8][CH2:9][CH2:10][N:11]3[C:15]([CH3:17])([CH3:16])[C:14](=[O:18])[NH:13][C:12]3=[O:19])[N:4]=2)=[CH:24][CH:23]=1

Participants

7

Reactant 2

HCID 66827Phenylboronic AcidHCID 602044701-{2-[5-Bromo-4-(5-chlorothiophen-2-yl)pyrimidin-2-ylamino]ethyl}-5,5-dimethylimidazolidine-2,4-dione

Product 1

HCID 602044851-{2-[4-(5-Chlorothiophen-2-yl)-5-phenylpyrimidin-2-ylamino]ethyl}-5,5-dimethylimidazolidine-2,4-dione

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A biphasic mixture of 30 mg (0.068 mmol) of 1-{2-[5-bromo-4-(5-chlorothiophen-2-yl)pyrimidin-2-ylamino]ethyl}-5,5-dimethylimidazolidine-2,4-dione, 10 mg (0.081 mmol) of phenylboronic acid, 4.0 mg (0.0034 mmol) of tetrakis(triphenylphosphine)palladium(0) in 2 mL of 1,4-dioxane and 0.5 mL of 2 M aqueous Na2CO3 was heated in a microwave at 140° C. for 20 min. The reaction mixture was cooled to rt, diluted with 5 mL of water and extracted twice with CH2Cl2 and twice with a 3:1 mixture of CHCl3 and iPrOH. The combined organic extracts were concentrated and the crude products separated by C-18 prep HPLC to give 1-{2-[4-(5-chlorothiophen-2-yl)-5-phenylpyrimidin-2-ylamino]ethyl}-5,5-dimethylimidazolidine-2,4-dione: MS (M+H)+ 442; and 5,5-dimethyl-1-{2-[5-phenyl-4-(5-phenylthiophen-2-yl)pyrimidin-2-ylamino]ethyl}imidazolidine-2,4-dione: MS (M+H)+ 484.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionextracted twice with CH2Cl2 and twice with a 3:1 mixture of CHCl3 and iPrOH
  3. concentrationThe combined organic extracts were concentrated
  4. customthe crude products separated by C-18 prep HPLC

Sources & evidence

ORD record
ord-59ee5bd4dbe44e91bdd46e560afc9244
Source dataset
uspto-grants-2010_08
Patent number
US07786132B2

Reaction notes

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