Acetic Acid → 2-(2-Chloro-4-iodo-pyridin-3-yl)-6-(7-ethyl-2,7-diaza-spiro[4.4]non-2-yl)-4-methyl-1H-benzoimidazole

HRID 470304Notes

Reaction equation

HRID 470304 reaction equation
[CH2:1]([N:3]1[CH2:22][CH2:21][C:5]2([CH2:9][N:8]([C:10]3[CH:15]=[C:14]([N+:16]([O-])=O)[C:13]([NH2:19])=[C:12]([CH3:20])[CH:11]=3)[CH2:7][CH2:6]2)[CH2:4]1)[CH3:2].C(O)(=O)C.[Cl:27][C:28]1[C:33]([CH:34]=O)=[C:32]([I:36])[CH:31]=[CH:30][N:29]=1>CO.[Pd]>[Cl:27][C:28]1[C:33]([C:34]2[NH:16][C:14]3[CH:15]=[C:10]([N:8]4[CH2:7][CH2:6][C:5]5([CH2:21][CH2:22][N:3]([CH2:1][CH3:2])[CH2:4]5)[CH2:9]4)[CH:11]=[C:12]([CH3:20])[C:13]=3[N:19]=2)=[C:32]([I:36])[CH:31]=[CH:30][N:29]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 100386372-Chloro-4-iodopyridine-3-carbaldehydeHCID 597852714-(7-Ethyl-2,7-diaza-spiro[4.4]non-2-yl)-2-methyl-6-nitro-phenylamine

Product 1

HCID 597851092-(2-Chloro-4-iodo-pyridin-3-yl)-6-(7-ethyl-2,7-diaza-spiro[4.4]non-2-yl)-4-methyl-1H-benzoimidazoleYield 86.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 4-(7-ethyl-2,7-diaza-spiro[4.4]non-2-yl)-2-methyl-6-nitro-phenylamine (304 mg, 1.0 mmol) in MeOH (47.5 mL) were added Pd/C (10%, 40 mg) and acetic acid (2.5 mL). The mixture was stirred under atmospheric hydrogen (balloon) at the room temperature for 3 h and then filter over Celite. The filtrate was mixed with 2-chloro-3-formyl-4-iodopyridine (267.5 mg, 1.0 mmol), stirred at the room temperature for 18 h, and evaporated to dryness under reduced pressure. The residue was dissolved in MeOH (10 mL) and 28% aqueous NH4OH solution (0.5 mL) was added. After it was stirred for 5 min, the mixture was concentrated and chromatographed (5:1, CH2Cl2/MeOH) to afford the title compound (450 mg, 86%). 1H NMR (MeOH-d4) δ 1.38 (t, J=8 Hz, 3H), 2.10-2.21 (4H), 2.56 (s, 3H), 3.28-3.57 (10H), 6.55 (s, 1H), 6.57 (s, 1H), 8.03 (d, J=6 Hz, 1H), 8.13 (d, J=6 Hz, 1H). ESI-MS m/z 522 (MH+).

Workup

  1. filtrationfilter over Celite
  2. stirringstirred at the room temperature for 18 h
  3. customevaporated to dryness under reduced pressure
  4. dissolutionThe residue was dissolved in MeOH (10 mL)
  5. addition28% aqueous NH4OH solution (0.5 mL) was added
  6. stirringAfter it was stirred for 5 min
  7. concentrationthe mixture was concentrated
  8. customchromatographed (5:1, CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-14d27f428f134c43b9068e96ac4b4d5d
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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