Acetic Acid → N-{4-[(2-{[2-fluoro-5-(trifluoromethyl)phenyl]amino}-1-methyl-1H-benzimidazol-5-yl)oxy]pyridin-2-yl}-3-(1-methylpiperidin-4-yl)propanamide

HRID 30789Notes

Reaction equation

HRID 30789 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13]1[N:17]([CH3:18])[C:16]2[CH:19]=[CH:20][C:21]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([NH:30][C:31](=[O:40])[CH2:32][CH2:33][CH:34]4[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]4)[CH:25]=3)=[CH:22][C:15]=2[N:14]=1.C=O.[C:43](O)(=O)C.C([BH3-])#N.[Na+]>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:9])([F:11])[F:10])=[CH:4][C:3]=1[NH:12][C:13]1[N:17]([CH3:18])[C:16]2[CH:19]=[CH:20][C:21]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([NH:30][C:31](=[O:40])[CH2:32][CH2:33][CH:34]4[CH2:35][CH2:36][N:37]([CH3:43])[CH2:38][CH2:39]4)[CH:25]=3)=[CH:22][C:15]=2[N:14]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 59790277N-{4-[(2-{[2-fluoro-5-(trifluoromethyl)phenyl]amino}-1-methyl-1H-benzimidazol-5-yl)oxy]pyridin-2-yl}-3-piperidin-4-ylpropanamide

Product 1

HCID 59790233N-{4-[(2-{[2-fluoro-5-(trifluoromethyl)phenyl]amino}-1-methyl-1H-benzimidazol-5-yl)oxy]pyridin-2-yl}-3-(1-methylpiperidin-4-yl)propanamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To N-{4-[(2-{[2-fluoro-5-(trifluoromethyl)phenyl]amino}-1-methyl-1H-benzimidazol-5-yl)oxy]pyridin-2-yl}-3-piperidin-4-ylpropanamide (1 eq) in methanol was added formalin (2 eq) and acetic acid(5%) followed by sodium cyanoborohydride (2 eq) and the resulting mixture was stirred at ambient temperature for 3 h. LC/MS showed formation of the product. The crude mixture was then concentrated and to it was added sodium bicarbonate and the resulting mixture was partitioned between ethyl acetate and water. The organic layer was dried with sodium sulfate and purified by preparative chromatography to yield N-{4-[(2-{[2-fluoro-5-(trifluoromethyl)phenyl]amino}-1-methyl-1H-benzimidazol-5-yl)oxy]pyridin-2-yl}-3-(1-methylpiperidin-4-yl)propanamide. MS: MH+=571.6.

Workup

  1. concentrationThe crude mixture was then concentrated and to it
  2. additionwas added sodium bicarbonate
  3. customthe resulting mixture was partitioned between ethyl acetate and water
  4. dry with materialThe organic layer was dried with sodium sulfate
  5. custompurified by preparative chromatography

Sources & evidence

ORD record
ord-7c258934c9134825b2591b017b22c2ba
Source dataset
uspto-grants-2008_09
Patent number
US07423150B2

Reaction notes

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