2-Methoxyethylamine → [3-(4-Fluorophenyl)(1h-indazol-5-yl)]-n-(2-methoxyethyl)carboxamide

HRID 1273047Notes

Reaction equation

HRID 1273047 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]([OH:19])=O)[CH:15]=3)[NH:10][N:9]=2)=[CH:4][CH:3]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:43][O:44][CH2:45][CH2:46][NH2:47]>O1CCCC1.O.CN(C)C=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]([NH:47][CH2:46][CH2:45][O:44][CH3:43])=[O:19])[CH:15]=3)[NH:10][N:9]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 80182-MethoxyethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 222607223-(4-Fluorophenyl)-1H-Indazole-5-Carboxylic Acid

Product 1

HCID 20789052[3-(4-Fluorophenyl)(1h-indazol-5-yl)]-n-(2-methoxyethyl)carboxamideYield 66.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared as described in Example 76. To a solution of 3-(4-fluorophenyl)-1H-indazole-5-carboxylic acid (0.200 g, 0.781 mmol) in tetrahydrofuran (5 mL) was added 1-hydroxybenzotriazole hydrate (0.316 g, 2.34 mmol) followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.449 g, 2.34 mmol), 2-methoxyethylamine (0.203 mL, 2.34 mmol) and N,N-dimethylformamide (2 mL). The solution was stirred for 16 h at room temperature. Water (40 mL) was added and the reaction mixture was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by preparative HPLC (10–90% acetonitrile/water). The pure fractions were made basic with ammonium hydroxide, and the solution evaporated under reduced pressure, diluted with water and filtered to give the title compound (0.162 g, 66% yield): 1H NMR (DMSO-d6) δ 13.45 (s, 1H), 8.70 (t, 1H), 8.56 (s, 1H), 8.08 (AB quartet, 2H), 7.92 (dd, 1H), 7.63 (d, 1H), 7.40 (t, 2H), 3.49 (s, 3H), 3.34 (m, 2H), 3.28 (s, 2H); ES-MS (m/z) 314 [M+1]+.

Workup

  1. customThe title compound was prepared
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by preparative HPLC (10–90% acetonitrile/water)
  7. customthe solution evaporated under reduced pressure
  8. additiondiluted with water
  9. filtrationfiltered

Sources & evidence

ORD record
ord-be115c5dc36d4ee28b9064981f6f6cd0
Source dataset
uspto-grants-2007_04
Patent number
US07208513B2

Reaction notes

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