Potassium Phosphate, Tribasic → 1-(5-(6-Bromopyridazin-4-yl)-7-(pyridin-2-yl)benzothiazol-2-yl)-3-ethylurea

HRID 712179Notes

Reaction equation

HRID 712179 reaction equation
[Br:1][C:2]1[N:3]=[N:4][CH:5]=[C:6](Br)[CH:7]=1.[CH2:9]([NH:11][C:12](=[O:32])[NH:13][C:14]1[S:15][C:16]2[C:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)=[CH:21][C:20](B(O)O)=[CH:19][C:17]=2[N:18]=1)[CH3:10].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Br:1][C:2]1[N:3]=[N:4][CH:5]=[C:6]([C:20]2[CH:21]=[C:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[C:16]3[S:15][C:14]([NH:13][C:12]([NH:11][CH2:9][CH3:10])=[O:32])=[N:18][C:17]=3[CH:19]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 441823363,5-DibromopyridazineHCID 727244832-(3-Ethylureido)-7-(pyridin-2-yl)benzothiazol-5-ylboronic acid

Product 1

HCID 866639621-(5-(6-Bromopyridazin-4-yl)-7-(pyridin-2-yl)benzothiazol-2-yl)-3-ethylureaYield 85.2%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3,5-dibromopyridazine (0.32 g, 1.34 mmol) in DMF (5 mL) was added 2-(3-ethylureido)-7-(pyridin-2-yl)benzothiazol-5-ylboronic acid (0.46 g, 1.34 mmol) and aqueous solution of K3PO4 (0.43 g, 2.01 mmol). The reaction was degassed by purging N2 for 15 min followed by addition of bis(triphenylphosphine)palladium (II) chloride (0.11 g, 0.13 mmol). The reaction mixture was again degassed for 10-15 min then heated up to 80° C. for 2-3 h. After reaction completion (by TLC), the mixture was poured onto crushed ice and extracted with EtOAc (3×50 mL). The combined organics were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified over 100-200 M silica-gel by using 3% MeOH-DCM to obtain the desired product as off-white solid (0.52 g, 85%). 1H NMR (DMSO-d6): δ 10.71 (s, 1H), 9.94 (m, 2H), 8.82 (m, 1H), 8.55 (d, J=8.0 Hz, 1H), 8.38 (s, 1H), 8.21 (s, 1H), 8.02 (t, J=8.0 Hz, 1H), 7.46 (m, 1H), 7.17 (br s, 1H), 3.22 (q, J=7.20 Hz, 2H), and 1.11 (t, J=7.20 Hz, 3H).

Workup

  1. customThe reaction was degassed
  2. customby purging N2 for 15 min
  3. customThe reaction mixture was again degassed for 10-15 min
  4. customAfter reaction completion (by TLC)
  5. additionthe mixture was poured
  6. customonto crushed ice
  7. extractionextracted with EtOAc (3×50 mL)
  8. washThe combined organics were washed with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customThe crude residue was purified over 100-200 M silica-gel

Sources & evidence

ORD record
ord-6497eaeed1644c57bb1ac8a2baa5ecdd
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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