Thiourea → n-[4-({2-[(3-Tert-butylphenyl)amino]-1-methyl-1h-benzimidazol-5-yl}oxy)pyridin-2-yl]-n'-(2-morpholin-4-ylethyl)urea

HRID 30795Notes

Reaction equation

HRID 30795 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:37]=[CH:38][C:39]=1NC)[O:18][C:19]1[CH:24]=[CH:23][N:22]=[C:21]([NH:25][C:26]([NH:28][CH2:29][CH2:30][N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[O:27])[CH:20]=1.[NH2:42][C:43]([NH2:45])=S>CO>[C:4]([C:8]1[CH:13]=[C:12]([NH:42][C:43]2[N:45]([CH3:2])[C:39]3[CH:38]=[CH:37][C:17]([O:18][C:19]4[CH:24]=[CH:23][N:22]=[C:21]([NH:25][C:26]([NH:28][CH2:29][CH2:30][N:31]5[CH2:32][CH2:33][O:34][CH2:35][CH2:36]5)=[O:27])[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 69006155n-{4-[3-Amino-4-(methylamino)phenoxy] (2-pyridyl)}[(2-morpholin-4-ylethyl)amino]carboxamideHCID 178440816HCID 178440816, compound

Product 1

HCID 59790199n-[4-({2-[(3-Tert-butylphenyl)amino]-1-methyl-1h-benzimidazol-5-yl}oxy)pyridin-2-yl]-n'-(2-morpholin-4-ylethyl)urea

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 3-(tert-butyl)benzenisothiocyanate (1 eq) in methanol was added N-{4-[3-amino-4-(methylamino)phenoxy](2-pyridyl)}[(2-morpholin-4-ylethyl)amino]carboxamide (1 eq) and the resulting mixture was stirred at ambient temperature for 16 h. LC/MS showed formation of corresponding thiourea. To this was added anhydrous ferric chloride (1.5 eq) and stirred for 3 h. The reaction mixture was then concentrated to half its volume and brought to neutral pH with 1N sodium hydroxide. It was then extracted with ethyl acetate and the organic layer was washed with brine and dried with sodium sulfate. The crude material was then purified on preparative chromatography to yield N-[4-({2-[(3 -tert-butylphenyl)amino]-1-methyl-1H-benzimidazol-5-yl}oxy)pyridin-2-yl]-N′-(2-morpholin-4-ylethyl)urea. MS: MH+=544.

Workup

  1. stirringstirred for 3 h
  2. concentrationThe reaction mixture was then concentrated to half its volume
  3. extractionIt was then extracted with ethyl acetate
  4. washthe organic layer was washed with brine
  5. dry with materialdried with sodium sulfate
  6. customThe crude material was then purified on preparative chromatography

Sources & evidence

ORD record
ord-c0ac4d88de934674ab369f7e17615636
Source dataset
uspto-grants-2008_09
Patent number
US07423150B2

Reaction notes

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