HCID 86698152, compound → HCID 86698153, compound

HRID 632870Notes

Reaction equation

HRID 632870 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}-1-1-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, 2 H) 1.13-1.22 (m, 5 H) 1.43-1.57 (m, 2H) 1.77-1.91 (m, 2 H) 2.11 (br. s, 1 H) 2.89-2.98 (m, 1 H) 3.81-3.90 (m, 1 H) 4.32-4.50 (m, 2 H) 5.40 (s, 2 H) 7.13 (dd, J=5.27, 0.75 Hz, 1 H) 7.23 (d, J=8.53 Hz, 1 H) 7.65 (d, J=8.28 Hz, 1 H) 8.34 (d, J=5.27 Hz, 1 H) 8.75 (s, 1 H); 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-fe116df0e0ad403c836f681d8ca73ccc
Source dataset
uspto-grants-2016_04
Patent number
US09321767B2

Reaction notes

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