Water → [3-(4-Fluorophenyl)(1h-indazol-5-yl)]-n-(3-methoxypropyl)carboxamide

HRID 1273014Notes

Reaction equation

HRID 1273014 reaction equation
C([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13](Cl)=[O:14])=[CH:10][CH:11]=2)[C:6]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[N:5]1)(=O)C.[CH3:23][O:24]C(C)CN.O.[N:30]1C=C[CH:33]=[CH:32][CH:31]=1>>[F:22][C:19]1[CH:18]=[CH:17][C:16]([C:6]2[C:7]3[C:12](=[CH:11][CH:10]=[C:9]([C:13]([NH:30][CH2:31][CH2:32][CH2:33][O:24][CH3:23])=[O:14])[CH:8]=3)[NH:4][N:5]=2)=[CH:21][CH:20]=1

Participants

5

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 126097192-Methoxypropan-1-amineHCID 224802271-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride

Product 1

HCID 20789057[3-(4-Fluorophenyl)(1h-indazol-5-yl)]-n-(3-methoxypropyl)carboxamideYield 35%

Procedure

The title compound was prepared as described in Example 68. To a solution of 1-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride (0.200 g, 0.632 mmol) in pyridine (4 mL) was added 2-methoxypropylamine (0.274 mL, 3.16 mmol). The solution was stirred for 3 h at room temperature. Water (40 mL) was added and the reaction mixture was extracted with ethyl acetate. The combined organic layers were washed with aqueous 1 N hydrochloric acid, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by preparative HPLC (10–90% acetonitrile/water). The pure fractions were basified with ammonium hydroxide, evaporated at reduced pressure, diluted with water and filtered to give the title compound (0.073 g, 35% yield): 1H NMR (DMSO-d6) δ 13.42 (br s, 1H), 8.60 (t, 1H), 8.53 (s, 1H), 8.07 (AB quartet, 2H), 7.92 (dd, 1H), 7.62 (d, 1H), 7.40 (t, 2H), 3.40 (t, 2H), 3.34 (m, 2H), 3.25 (s, 3H), 1.79 (m, 2H); ES-MS (m/z) 328 [M+1]+.

Workup

  1. customThe title compound was prepared
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. washThe combined organic layers were washed with aqueous 1 N hydrochloric acid
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by preparative HPLC (10–90% acetonitrile/water)
  8. customevaporated at reduced pressure
  9. additiondiluted with water
  10. filtrationfiltered

Sources & evidence

ORD record
ord-eb2f7cdaeb9b469d83120a14020bfb39
Source dataset
uspto-grants-2007_04
Patent number
US07208513B2

Reaction notes

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