Dimethylamine, hydrochloride → N-(2-aminophenyl)-2-(1-ethyl-6-fluoro-4-hydroxy-1-H-indol-3-yl) acetamide

HRID 1404101Notes

Reaction equation

HRID 1404101 reaction equation
[CH2:1]([N:3]1[C:11]2[C:6](=[C:7]([OH:13])[CH:8]=[C:9]([F:12])[CH:10]=2)[C:5]([CH2:14][C:15]([OH:17])=O)=[CH:4]1)[CH3:2].CN(C(ON1N=[N:33][C:28]2[CH:29]=[CH:30][CH:31]=[N:32][C:27]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N(C)[CH3:43].Cl.CCN(C(C)C)C(C)C>C1COCC1>[NH2:32][C:27]1[CH:43]=[CH:31][CH:30]=[CH:29][C:28]=1[NH:33][C:15](=[O:17])[CH2:14][C:5]1[C:6]2[C:11](=[CH:10][C:9]([F:12])=[CH:8][C:7]=2[OH:13])[N:3]([CH2:1][CH3:2])[CH:4]=1

Participants

6

Reactant 4

HCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 583039722-(1-ethyl-6-fluoro-4-hydroxy-1H-indol-3-yl)acetic acid

Product 1

HCID 68322751N-(2-aminophenyl)-2-(1-ethyl-6-fluoro-4-hydroxy-1-H-indol-3-yl) acetamideYield 53.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The solution of 11-3 (440 mg, 1.85 mmol), HATU (850 g, 2.23 mmol), HNMe2.HCl (150 g, 1.84 mmol) in THF (5 mL) was added DIPEA (600 mg, 4.63 mmol) dropwise at 0° C. The reaction temperature was allowed to raise room temperature and stirred overnight. The volatile was removed by evaporation. A white residue was obtained, which was quenched with 100 mL of water and extracted with DCM (50 mL×4). The combined organic layers were dried over anhydrous Na2SO4. After filtration and concentration, the residue was purified by silica gel chromatography (elution with petroleum:ethyl acetate: 1:1) to get 12-2 (324 mg, 53.5%) as a white solid. LCMS: calc 327.4 and found 328.1 [MH]+.

Workup

  1. customThe volatile was removed by evaporation
  2. customA white residue was obtained
  3. customwhich was quenched with 100 mL of water
  4. extractionextracted with DCM (50 mL×4)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified by silica gel chromatography (elution with petroleum:ethyl acetate: 1:1)

Sources & evidence

ORD record
ord-40e5b0c43f1c4ddf9401aa57bc5f3b0b
Source dataset
uspto-grants-2014_12
Patent number
US08912220B2

Reaction notes

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