Sodium hydride → 6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylthio)benzo[d]thiazole

HRID 1847960Notes

Reaction equation

HRID 1847960 reaction equation
[N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[NH:3][CH:2]=1.[H-].[Na+].Cl[CH2:13][C:14]1[CH:24]=[CH:23][C:17]2[N:18]=[C:19]([S:21][CH3:22])[S:20][C:16]=2[CH:15]=1>CN(C=O)C>[N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]([CH2:13][C:14]2[CH:24]=[CH:23][C:17]3[N:18]=[C:19]([S:21][CH3:22])[S:20][C:16]=3[CH:15]=2)[CH:2]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 866809946-(Chloromethyl)-2-(methylthio)benzo[d]thiazoleHCID 178420746HCID 178420746, compound

Product 1

HCID 866809966-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylthio)benzo[d]thiazoleYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3H-imidazo[4,5-b]pyridine (2.99 g, 25 mmol) in DMF (100 mL) was added sodium hydride (60% in mineral oil, 1.0 g, 25 mmol) slowly at 0° C. After the reaction mixture was stirred at rt for 20 min, it was treated with a solution of 6-(chloromethyl)-2-(methylthio)benzo[d]thiazole from Step 3 of this Example (4.8 g, 21 mmol) in DMF (20 mL) at 0° C. The reaction mixture was then stirred at rt overnight. The mixture was quenched with 3 mL of saturated aq NH4Cl and concentrated under reduced pressure. The residue was diluted with 600 mL of EtOAc and washed with water and brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure The crude product was purified on a silica gel column using a mixture of MeOH—CH2Cl2 (1:30, v/v) as eluent to give 6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylthio)benzo[d]thiazole as a tan solid (2.5 g, 38%). The regiochemistry of the alkylation was determined by a 2-dimensional nuclear Overhauser effect (NOE) experiment. 1H NMR (300 MHz, DMSO-d6) δ 8.65 (s, 1H), 8.38 (dd, J=1.2, 4.8 Hz, 1H), 8.11 (dd, J=1.3, 8.1 Hz, 1H), 8.00 (d, J=1.1 Hz, 1H), 7.81 (d, J=8.3 Hz, 1H), 7.46 (dd, J=1.6, 8.4 Hz, 1H), 7.30 (dd, J=4.8, 8.0 Hz, 1H), 5.62 (s, 2H), 2.77 (s, 3H). LCMS (ESI) m/z 313 (M+H)+.

Workup

  1. stirringThe reaction mixture was then stirred at rt overnight
  2. customThe mixture was quenched with 3 mL of saturated aq NH4Cl
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was diluted with 600 mL of EtOAc
  5. washwashed with water and brine
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated under reduced pressure The crude product
  8. customwas purified on a silica gel column
  9. additiona mixture of MeOH—CH2Cl2 (1:30, v/v) as eluent

Sources & evidence

ORD record
ord-74c619e531b944d4889127fb2104bde5
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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