Nitrogen → 1-(6-Bromo-4-(pyridin-2-yl)thiazolo[5,4-c]pyridin-2-yl)-3-ethylurea

HRID 712314Notes

Reaction equation

HRID 712314 reaction equation
Br[C:2]1[C:7]2[S:8][C:9]([NH:11][C:12]([NH:14][CH2:15][CH3:16])=[O:13])=[N:10][C:6]=2[CH:5]=[C:4]([Br:17])[N:3]=1.C([Sn](CCCC)(CCCC)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1)CCC.N#N>CN(C=O)C.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>[Br:17][C:4]1[N:3]=[C:2]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[C:7]2[S:8][C:9]([NH:11][C:12]([NH:14][CH2:15][CH3:16])=[O:13])=[N:10][C:6]=2[CH:5]=1

Participants

6

Reactant 3

HCID 947NitrogenHCID 6077842-(Tributylstannyl)pyridineHCID 580332371-(4,6-Dibromothiazolo[5,4-c]pyridin-2-yl)-3-ethylurea2×

Product 1

HCID 866640261-(6-Bromo-4-(pyridin-2-yl)thiazolo[5,4-c]pyridin-2-yl)-3-ethylurea

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 1-(4,6-dibromothiazolo[5,4-c]pyridin-2-yl)-3-ethylurea (Intermediate 8) (0.25 g, 0.65 mmol) and 2-(tributylstannyl)pyridine (0.21 mL, 0.65 mmol) in DMF (10 mL) was purged with N2 for 15 min followed by addition of tetrakis(triphenylphosphine)palladium (0) (0.075 g, 0.065 mmol). The reaction mixture was again degassed by purging N2 for 15 min then heated to 80° C. for 16 h. The solvent was distilled under reduced pressure, water (25 mL) added and extracted with EtOAc (3×100 mL). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified over silica gel (100-200M, 2.50% MeOH-DCM) to afford the desired product that was finally triturated with ether (0.10 g, 40%). The regio chemistry was ascertained by NOE experiments.

Workup

  1. customThe reaction mixture was again degassed
  2. customby purging N2 for 15 min
  3. distillationThe solvent was distilled under reduced pressure, water (25 mL)
  4. additionadded
  5. extractionextracted with EtOAc (3×100 mL)
  6. dry with materialThe combined organics were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified over silica gel (100-200M, 2.50% MeOH-DCM)

Sources & evidence

ORD record
ord-427a4618b4174d189d8dda0a636d29c6
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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