Triethylamine → 5-(2-(((4-(3-Methylcarbamoylpropyl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide

HRID 2215519Notes

Reaction equation

HRID 2215519 reaction equation
[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]([N:24]4[CH2:29][CH2:28][CH:27]([CH2:30][CH2:31][CH2:32][C:33]([OH:35])=O)[CH2:26][CH2:25]4)=[O:23])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4].Cl.CN.F[P-](F)(F)(F)(F)F.[N:46]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:50]2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O>[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]([N:24]4[CH2:29][CH2:28][CH:27]([CH2:30][CH2:31][CH2:32][C:33](=[O:35])[NH:46][CH3:50])[CH2:26][CH2:25]4)=[O:23])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 6364545Methylamine hydrochlorideHCID 219493124-(1-((4-(1-Methylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonyl)piperidin-4-yl)butyric acid

Product 1

HCID 104133425-(2-(((4-(3-Methylcarbamoylpropyl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamideYield 17.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(1-((4-(1-Methylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonyl)piperidin-4-yl)butyric acid (170 mg, 0.35 mmol) was dissolved in N,N-dimethylformamide (7.0 ml); methylamine hydrochloride (48 mg, 0.71 mmol), benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (314 mg, 0.71 mmol) and triethylamine (0.35 ml) were added thereto; and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia NH silica gel, hexane-ethyl acetate-methanol system). After a small amount of acetone and ethyl acetate were added to the obtained amorphous solid; this solution was diluted with diethyl ether; and the solid portion was filtered off, washed with diethyl ether, and dried under aeration to yield the title compound (30 mg, 0.061 mmol, 17%) as a colorless amorphous solid.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (Fuji Silysia NH silica gel, hexane-ethyl acetate-methanol system)
  6. additionAfter a small amount of acetone and ethyl acetate were added to the obtained amorphous solid
  7. additionthis solution was diluted with diethyl ether
  8. filtrationand the solid portion was filtered off
  9. washwashed with diethyl ether
  10. customdried under aeration

Sources & evidence

ORD record
ord-745fdd7541d9424fb6909468c982e9ea
Source dataset
uspto-grants-2006_09
Patent number
US07109219B2

Reaction notes

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