Thiourea → N-[4-({2-[(3-tert-butylphenyl)amino]-1-methyl-1H-benzimidazol-5-yl}oxy)pyridin-2-yl]-2-(4-methylpiperidin-1-yl)acetamide

HRID 1963735Notes

Reaction equation

HRID 1963735 reaction equation
[N-]=[C:2]=S.[C:4]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)([CH3:7])([CH3:6])[CH3:5].[NH2:14][C:15]1[CH:16]=[C:17]([CH:36]=[CH:37][C:38]=1NC)[O:18][C:19]1[CH:24]=[CH:23][N:22]=[C:21]([NH:25][C:26](=[O:35])[CH2:27][N:28]2[CH2:33][CH2:32][CH:31]([CH3:34])[CH2:30][CH2:29]2)[CH:20]=1.[NH2:41][C:42]([NH2:44])=S>CO>[C:4]([C:8]1[CH:13]=[C:12]([NH:41][C:42]2[N:44]([CH3:2])[C:38]3[CH:37]=[CH:36][C:17]([O:18][C:19]4[CH:24]=[CH:23][N:22]=[C:21]([NH:25][C:26](=[O:35])[CH2:27][N:28]5[CH2:29][CH2:30][CH:31]([CH3:34])[CH2:32][CH2:33]5)[CH:20]=4)=[CH:16][C:15]=3[N:14]=2)[CH:11]=[CH:10][CH:9]=1)([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 2723790ThioureaHCID 59789988N-{4-[3-amino-4-(methylamino)phenoxy](2-pyridyl)}-2-(4-methylpiperidyl)acetamideHCID 178440816HCID 178440816, compound

Product 1

HCID 59790090N-[4-({2-[(3-tert-butylphenyl)amino]-1-methyl-1H-benzimidazol-5-yl}oxy)pyridin-2-yl]-2-(4-methylpiperidin-1-yl)acetamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-(tert-Butyl)benzenisothiocyanate was added to a solution of N-{4-[3-amino-4-(methylamino)phenoxy](2-pyridyl)}-2-(4-methylpiperidyl)acetamide in methanol. Reaction was stirred at room temperature for 15 hours. Thiourea formation was confirmed by LC/MS. Ferric chloride was added and the resulting mixture was stirred at room temperature for 4 hours. After cyclization was complete by LC/MS the reaction mixture was concentrated and aqueous sodium carbonate was added until basic pH. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water then brine, and dried over sodium sulfate and concentrated. The crude product was purified by reverse phase HPLC. MS: MH+=527.2.

Workup

  1. customReaction
  2. stirringthe resulting mixture was stirred at room temperature for 4 hours
  3. concentrationwas concentrated
  4. additionaqueous sodium carbonate was added until basic pH
  5. customThe reaction mixture was partitioned between ethyl acetate and water
  6. washThe organic layer was washed with water
  7. dry with materialbrine, and dried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-ece16306258b41dfb7681b4c0a795d14
Source dataset
uspto-grants-2013_04
Patent number
US08415382B2

Reaction notes

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