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

HRID 470305Notes

Reaction equation

HRID 470305 reaction equation
[CH2:1]([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)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=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]>[CH2:1]([N:8]1[CH2:29][CH2:28][CH2:27][C:10]2([CH2:11][CH2:12][CH2:13][N:14]([C:16]3[CH:17]=[C:18]([CH3:26])[C:19]4[N:25]=[C:41]([C:40]5[C:35]([Cl:34])=[N:36][CH:37]=[CH:38][C:39]=5[I:43])[NH:22][C:20]=4[CH:21]=3)[CH2:15]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=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 597853632-Benzyl-8-[2-(2-chloro-4-iodo-pyridin-3-yl)-7-methyl-3H-benzoimidazol-5-yl]-2,8-diaza-spiro[5.5]undecaneYield 9%

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 (330:10:1 CH2Cl2/MeOH/28% aqueous NH4OH) to afford the title compound (55 mg, 9%). 1H NMR (CDCl3) δ 1.22-1.36 (2H), 1.49-1.84 (6H), 1.95-2.59 (6H), 2.59 (s, 3H), 2.94-3.45 (6H), 6.82 (s, 1H), 6.87 (s, 1H), 7.16-7.33 (5H), 7.72 (d, J=6 Hz, 1H), 7.99 (d, J=6 Hz, 1H). ESI-MS m/z 612 (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 (330:10:1 CH2Cl2/MeOH/28% aqueous NH4OH)

Sources & evidence

ORD record
ord-7cf9beba22eb4dcaa19b856adb124175
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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