HCID 86698152, compound → HCID 86698153, compound

HRID 1424501Notes

Reaction equation

HRID 1424501 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[N:8]=[C:9]([CH2:16][N:17]3[C:21]4[CH:22]=[N:23][CH:24]=[CH:25][C:20]=4[N:19]([CH:26]4[CH2:28][CH2:27]4)[C:18]3=[O:29])[N:10]([CH2:11][CH2:12][CH2:13][CH:14]=[O:15])[C:5]2=[CH:4][CH:3]=1.[CH3:30][Mg]I>C1COCC1.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[N:7]=[C:6]2[N:8]=[C:9]([CH2:16][N:17]3[C:21]4[CH:22]=[N:23][CH:24]=[CH:25][C:20]=4[N:19]([CH:26]4[CH2:28][CH2:27]4)[C:18]3=[O:29])[N:10]([CH2:11][CH2:12][CH2:13][CH:14]([OH:15])[CH3:30])[C:5]2=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 86698152HCID 86698152, compoundHCID 178418373HCID 178418373, compound

Product 1

HCID 86698153HCID 86698153, compoundYield 22.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
-20 °C

Procedure

In a 100 mL dry flask, 4-{5-chloro-2-[(1-cyclopropyl-2-oxo-1,2-dihydro-3H-imidazo[4,5-c]pyridin-3-yl)methyl]-1H-imidazo[4,5-b]pyridin-1-yl}butanal 67-1 (1.5 g, 3.6 mmol) was dissolved in dry THF (50 mL) and cooled until −20° C. under N2 atmosphere. An excess methylmagnesium iodide (3M in THF) (1.8 mL, 5.5 mmol, 1.5 eq.) was then gently added dropwise to the cooled solution via syringe. The solution was warmed up until ambient temperature and stirred for 4 hours. The solution was diluted with 30 mL NaHCO3 solution and extracted with EtOAC (30 mL). The combined organics were dried (MgSO4) and concentrated in vacuo. The crude was purified on RP SunFire Prep column (C18 OBD-10 μm, 30×150 mm), using a 0.25% NH4HCO3 solution in water-MeOH solution to give 350 mg (22%) of 3-{[5-chloro-1-(4-hydroxypentyl)-1H-imidazo[4,5-b]pyridin-2-yl]methyl}-1-cyclopropyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (67) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.99-1.05 (m, 2H) 1.13-1.22 (m, 5H) 1.43-1.57 (m, 2H) 1.77-1.91 (m, 2H) 2.11 (br. s, 1H) 2.89-2.98 (m, 1H) 3.81-3.90 (m, 1H) 4.32-4.50 (m, 2H) 5.40 (s, 2H) 7.13 (dd, J=5.27, 0.75 Hz, 1H) 7.23 (d, J=8.53 Hz, 1H) 7.65 (d, J=8.28 Hz, 1H) 8.34 (d, J=5.27 Hz, 1H) 8.75 (s, 1H); LCMS m/z=427 (M+H)+

Workup

  1. customIn a 100 mL dry flask
  2. temperatureThe solution was warmed up until ambient temperature
  3. extractionextracted with EtOAC (30 mL)
  4. dry with materialThe combined organics were dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude was purified on RP SunFire Prep column (C18 OBD-10 μm, 30×150 mm)

Sources & evidence

ORD record
ord-1f76feee475243e08c4e5b0745e5e0d8
Source dataset
uspto-grants-2015_01
Patent number
US08927720B2

Reaction notes

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