Sodium Carbonate → HCID 20594031, compound

HRID 1369416Notes

Reaction equation

HRID 1369416 reaction equation
Br[C:2]1[N:3]=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[N:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[N:8]=2)[CH:6]=1.[S:29]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:4]2[N:5]([C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C@H:14]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:15])[N:8]=3)[CH:6]=[C:2]([C:31]3[CH:32]=[CH:33][S:29][CH:30]=3)[N:3]=2)=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 10340Sodium Carbonate2×HCID 581760Thiophene-3-boronic acidHCID 20594053HCID 20594053, compound

Product 1

HCID 20594031HCID 20594031, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

4-Bromo-2-(4-fluorophenyl)-1-(2-[1-(S)-phenylethyl]amino-4-pyrimidyl)imidazole (109 mg, 0.25 mmol), thiophene-3-boronic acid (35 mg; 0.27 mmol) and Pd(PPh3)4 (14 mg, 0.0125 mmol) are dissolved in dioxane (1.25 ml) and saturated Na2CO3 solution (0.33 ml, 0.5 mmol) and heated to 80 C for 18 h. The reaction mixture is poured on saturated Na2CO3 solution and extracted with ethyl acetate three times. The combined organic phases are dried over Na2SO4, filtered and evaporated and purified via preparative HPLC on LiChrospher RP-18 (Gilson HPLC-system; column tube: 125 mm×25 mm ID) with MeCN/water as elution system, 40:60 to 100:0 as gradient and a flow rate of 10 ml/min to yield the title product as colorless crystals (62 mg, 60%).

Workup

  1. extractionextracted with ethyl acetate three times
  2. dry with materialThe combined organic phases are dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. custompurified via preparative HPLC on LiChrospher RP-18 (Gilson HPLC-system; column tube: 125 mm×25 mm ID) with MeCN/water as elution system, 40:60 to 100:0 as gradient

Sources & evidence

ORD record
ord-ffa2c0b63f0e455490fe500356a79dc1
Source dataset
uspto-grants-2003_06
Patent number
US06579874B2

Reaction notes

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