Acetic Acid → 2-[2-(2-Chloro-4-iodo-pyridin-3-yl)-7-methyl-3H-benzoimidazol-5-yl]-2,8-diaza-spiro[5.5]undecane

HRID 470306Notes

Reaction equation

HRID 470306 reaction equation
C([N:8]1[CH2:29][CH2:28][CH2:27][C:10]2([CH2:15][N:14]([C:16]3[CH:21]=[C:20]([N+:22]([O-])=O)[C:19]([NH2:25])=[C:18]([CH3:26])[CH:17]=3)[CH2:13][CH2:12][CH2:11]2)[CH2:9]1)C1C=CC=CC=1.C(O)(=O)C.[Cl:34][C:35]1[C:40]([CH:41]=O)=[C:39]([I:43])[CH:38]=[CH:37][N:36]=1>CO.[Pd]>[Cl:34][C:35]1[C:40]([C:41]2[NH:22][C:20]3[CH:21]=[C:16]([N:14]4[CH2:13][CH2:12][CH2:11][C:10]5([CH2:27][CH2:28][CH2:29][NH:8][CH2:9]5)[CH2:15]4)[CH:17]=[C:18]([CH3:26])[C:19]=3[N:25]=2)=[C:39]([I:43])[CH:38]=[CH:37][N:36]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 100386372-Chloro-4-iodopyridine-3-carbaldehydeHCID 597854884-(8-Benzyl-2,8-diaza-spiro[5.5]undec-2-yl)-2-methyl-6-nitro-phenylamine

Product 1

HCID 597849792-[2-(2-Chloro-4-iodo-pyridin-3-yl)-7-methyl-3H-benzoimidazol-5-yl]-2,8-diaza-spiro[5.5]undecaneYield 55.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 4-(8-benzyl-2,8-diaza-spiro[5.5]undec-2-yl)-2-methyl-6-nitro-phenylamine (394 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 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 (100:9:1 CH2Cl2/MeOH/28% aqueous NH4OH) to afford the title compound (288 mg, 55%). 1H NMR (CDCl3) δ 1.28-1.72 (8H), 2.57 (s, 3H), 2.57-3.12 (8H), 6.82 (s, 1H), 6.92 (s, 1H), 6.73 (d, J=6 Hz, 1H), 7.98 (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 (100:9:1 CH2Cl2/MeOH/28% aqueous NH4OH)

Sources & evidence

ORD record
ord-c90aee64913946b1be7ca2bcac4a3aca
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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