4-Iodo-2-methoxynicotinaldehyde → 2-(4-Iodo-2-methoxy-pyridin-3-yl)-4-methyl-6-morpholin-4-yl-1H-imidazo[4,5-c]pyridine

HRID 457560Notes

Reaction equation

HRID 457560 reaction equation
[CH3:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([NH2:11])[CH:5]=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[N:3]=1.[H][H].[I:20][C:21]1[CH:26]=[CH:25][N:24]=[C:23]([O:27][CH3:28])[C:22]=1[CH:29]=O>[Pd].CO>[I:20][C:21]1[CH:26]=[CH:25][N:24]=[C:23]([O:27][CH3:28])[C:22]=1[C:29]1[NH:11][C:6]2[CH:5]=[C:4]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[N:3]=[C:2]([CH3:1])[C:7]=2[N:8]=1

Participants

6

Reactant 3

HCID 100383814-Iodo-2-methoxynicotinaldehydeHCID 184399272-Methyl-6-morpholin-4-yl-3-nitro-pyridin-4-ylamineHCID 178418361HCID 178418361, compound

Product 1

HCID 184399252-(4-Iodo-2-methoxy-pyridin-3-yl)-4-methyl-6-morpholin-4-yl-1H-imidazo[4,5-c]pyridineYield 80%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent3×

Procedure

To 2-methyl-6-morpholin-4-yl-3-nitro-pyridin-4-ylamine (220 mg, 0.924 mmol) and 10% palladium on carbon (50 mg) were added methanol (10 mL) under nitrogen. The reaction mixture was stirred under hydrogen atmosphere (hydrogen balloon) for 18 hours. The solution was filtered through a pad of celite and the filtercake was washed with a small amount of MeOH. The product in MeOH was concentrated and used for the next step without purification; LCMS (+ESI, M+H+) m/z 209. To the crude diamino in MeOH (5 mL) was added a solution of 4-iodo-2-methoxy-pyridine-3-carbaldehyde (267 mg, 1.02 mmol) in MeOH (5 mL) at 0° C. and stirred for 0.5 hour. The resulting mixture was allowed to warm to ambient temperature and stirred for 4 days in an open system exposed to air. The reaction mixture was then heated to 50° C. and stirred for 2 days. MeOH was evaporated in vacuo and the crude was purified on silica gel column using CH2Cl2:MeOH (95:5 gradient) to give the title compound as a yellow solid (332 mg, 80%): IR (KBr, cm−1) 1624, 1554, 1458, 1378; 1H NMR (400 MHz, DMSO) δ 12.46 (s, 1H), 8.00 and 7.64 (d, J=5.5, 1H), 6.54 (s, 1H), 3.80 (s, 3H), 3.74–3.72 (m, 4H), 3.38–3.36 (m, 4H), 2.58 (s, 3H); LCMS (+ESI, M+H+) m/z 452; HPLC: 97% (220 nm).

Workup

  1. filtrationThe solution was filtered through a pad of celite
  2. washthe filtercake was washed with a small amount of MeOH
  3. concentrationThe product in MeOH was concentrated
  4. customused for the next step without purification
  5. stirringstirred for 4 days in an open system
  6. temperatureThe reaction mixture was then heated to 50° C.
  7. stirringstirred for 2 days
  8. customMeOH was evaporated in vacuo
  9. customthe crude was purified on silica gel column

Sources & evidence

ORD record
ord-8c5f404728e247a8bb6983f0f3597a96
Source dataset
uspto-grants-2007_03
Patent number
US07189716B2

Reaction notes

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