(6-Methoxypyridin-3-yl)boronic acid → 2-(4-Cyclopropylpiperazin-1-yl)-6-(6-methoxypyridin-3-yl)benzothiazole

HRID 1619250Notes

Reaction equation

HRID 1619250 reaction equation
Br[C:2]1[CH:19]=[CH:18][C:5]2[N:6]=[C:7]([N:9]3[CH2:14][CH2:13][N:12]([CH:15]4[CH2:17][CH2:16]4)[CH2:11][CH2:10]3)[S:8][C:4]=2[CH:3]=1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][N:23]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>C1COCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:15]1([N:12]2[CH2:13][CH2:14][N:9]([C:7]3[S:8][C:4]4[CH:3]=[C:2]([C:25]5[CH:24]=[N:23][C:22]([O:21][CH3:20])=[CH:27][CH:26]=5)[CH:19]=[CH:18][C:5]=4[N:6]=3)[CH2:10][CH2:11]2)[CH2:17][CH2:16]1

Participants

6

Reactant 3

HCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 595888036-Bromo-2-(4-cyclopropylpiperazin-1-yl)benzothiazole

Product 1

HCID 237288912-(4-Cyclopropylpiperazin-1-yl)-6-(6-methoxypyridin-3-yl)benzothiazole

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

To a solution of 6-bromo-2-(4-cyclopropylpiperazin-1-yl)benzothiazole (400 mg, 1.18 mmol) and 2-methoxy-5-pyridineboronic acid (217 mg, 1.42 mmol) in THF—H2O (16 mL, 5:1) was added Pd2(dba)3 (191 mg, 0.118 mmol), followed by P(t-Bu)3BF4 (68 mg, 0.236 mmol) and K3PO4.H2O (1.57 g, 5.9 mmol). The mixture was heated to 60° C. for 3 h. The mixture was filtered and the filtrate was evaporated. the residue was diluted with water (5 mL) and extracted with CH2Cl2 (3×5 mL). The combined organic extracts were dried (Na2SO4) and concentrated to give the crude product, which was purified by column chromatography on silica gel eluting with CH2Cl2/MeOH (1:50). This afforded 253 mg (58%) of 2-(4-cyclopropyl-piperazin-1-yl)-6-(6-methoxypyridin-3-yl)benzothiazole.

Workup

  1. filtrationThe mixture was filtered
  2. customthe filtrate was evaporated
  3. additionthe residue was diluted with water (5 mL)
  4. extractionextracted with CH2Cl2 (3×5 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-e26659a2c6724218aa93a63dd09159ec
Source dataset
uspto-grants-2014_07
Patent number
US08772285B2

Reaction notes

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