Methylamine → N-methyl-4-(1,4-dihydroindeno[1,2-c]pyrazol-3-yl)benzamide

HRID 990986Notes

Reaction equation

HRID 990986 reaction equation
[NH:1]1[C:5]2[C:6]3[C:11]([CH2:12][C:4]=2[C:3]([C:13]2[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=2)=[N:2]1)=[CH:10][CH:9]=[CH:8][CH:7]=3.CN.[N:24]1(C2C=CN=CC=2)CCC[CH2:25]1.C(N=C=NC(C)C)(C)C>C(O)C.ClCCl>[CH3:25][NH:24][C:17](=[O:18])[C:16]1[CH:15]=[CH:14][C:13]([C:3]2[C:4]3[CH2:12][C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:5]=3[NH:1][N:2]=2)=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 6329Methylamine2×HCID 12734Diisopropylcarbodiimide2×HCID 755674-Pyrrolidinopyridine2×HCID 184158474-(1,4-Dihydroindeno[1,2-c]pyrazol-3-yl)benzoic acid

Product 1

HCID 18415900N-methyl-4-(1,4-dihydroindeno[1,2-c]pyrazol-3-yl)benzamide

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-(1,4-dihydroindeno[1,2-c]pyrazol-3-yl)benzoic acid (0.8 g), methylamine in ethanol (0.27 ml of a 33% w/w solution), 4-pyrrolidinopyridine (0.47 g), diisopropylcarbodiimide (0.5 ml) and dichloromethane (30 ml) was stirred at ambient temperature for 20 hours. More methylamine in ethanol (0.3 ml of a 33% w/w solution), 4-pyrrolidinopyridine (0.5 g) and diisopropylcarbodiimide (1 ml) were added and the mixture was stirred for 3 hours at ambient temperature. The solvent was removed under reduced pressure at 50° C. The mixture was kept under vacuum for 2 hours and then dichloromethane (50 ml) was added. The mixture was stirred at ambient temperature for 20 hours and then allowed to stand for 72 hours. A solid was removed by filtration and purified by flash column chromatography on silica using toluene/acetic acid (10:1) and then ethyl acetate as the mobile phase to give N-methyl-4-(1,4-dihydroindeno[1,2-c]pyrazol-3-yl)benzamide, m.p. 182-188° C.

Workup

  1. stirringthe mixture was stirred for 3 hours at ambient temperature
  2. customThe solvent was removed under reduced pressure at 50° C
  3. waitThe mixture was kept under vacuum for 2 hours
  4. additiondichloromethane (50 ml) was added
  5. stirringThe mixture was stirred at ambient temperature for 20 hours
  6. waitto stand for 72 hours
  7. customA solid was removed by filtration
  8. custompurified by flash column chromatography on silica

Sources & evidence

ORD record
ord-59a585b89f614855994b1a5eb3f4aef3
Source dataset
uspto-grants-2002_10
Patent number
US06462036B1

Reaction notes

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