4-Iodo-2-methoxynicotinaldehyde → 4-[2-(4-Iodo-2-methoxy-pyridin-3-yl)-7-methyl-3H-benzoimidazol-5-yl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1793724Notes

Reaction equation

HRID 1793724 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18]([CH3:20])[C:17]([NH2:21])=[C:16]([NH2:22])[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[I:23][C:24]1[CH:29]=[CH:28][N:27]=[C:26]([O:30][CH3:31])[C:25]=1[CH:32]=O>CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18]([CH3:20])[C:17]3[N:21]=[C:32]([C:25]4[C:26]([O:30][CH3:31])=[N:27][CH:28]=[CH:29][C:24]=4[I:23])[NH:22][C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 100383814-Iodo-2-methoxynicotinaldehydeHCID 235419144-(3,4-Diamino-5-methyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 235419074-[2-(4-Iodo-2-methoxy-pyridin-3-yl)-7-methyl-3H-benzoimidazol-5-yl]-piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-(3,4-Diamino-5-methyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (44.6 mmol—assuming 100% conversion in previous step) in methanol (ca 2700 mL) at 0° C under a nitrogen atmosphere was slowly added (2 h) via addition funnel, a solution of 4-iodo-2-methoxy-pyridine-3-carbaldehyde (15.0 g, 57.1 mmol) in anhydrous methanol (225 mL). The resulting solution was then stirred at 0° C. for an additional 30 min, the cooling bath was removed, and the reaction mixture was allowed to stir at room temperature in the presence of air for 72 h. The resulting solution was concentrated in vacuo and the residue was dissolved in dichloromethane (1500 mL) and the solvent removed in vacuo (repeated 3×). The resulting dark foamy solid was dried under high vacuum. 1H NMR (500 MHz, CDCl3) δ 7.82 (d, 1H, J=5.4 Hz), 7.50 (d, 1H, J=5.4 Hz), 6.98 (brs, 1H), 6.90 (brs, 1H), 4.05 (s, 3H), 3.67–3.58 (m, 4H), 3.18–3.09 (m, 4H), 2.63 (s, 3H), 1.49 (s, 9H); LCMS (M+H)+ m/z 550.

Workup

  1. additionvia addition funnel
  2. customthe cooling bath was removed
  3. stirringto stir at room temperature in the presence of air for 72 h
  4. concentrationThe resulting solution was concentrated in vacuo
  5. dissolutionthe residue was dissolved in dichloromethane (1500 mL)
  6. customthe solvent removed in vacuo (repeated 3×)
  7. customThe resulting dark foamy solid was dried under high vacuum

Sources & evidence

ORD record
ord-94d85650d7304a0aa776d5e084ec41e8
Source dataset
uspto-grants-2006_07
Patent number
US07081454B2

Reaction notes

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