4-(4-Methylpiperazin-1-yl)benzoic acid → HCID 70982140, compound

HRID 1479192Notes

Reaction equation

HRID 1479192 reaction equation
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13](Cl)=[O:14])=[CH:11][CH:10]=2)[CH2:5][CH2:4]1.CN1CCN(C2C=CC(C(O)=O)=CC=2)CC1.[CH2:34]([O:41][CH2:42][CH2:43][O:44][C:45]1[CH:53]=[C:52]2[C:48]([C:49]([NH2:54])=[N:50][NH:51]2)=[CH:47][CH:46]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>N1C=CC=CC=1>[CH2:34]([O:41][CH2:42][CH2:43][O:44][C:45]1[CH:53]=[C:52]2[C:48]([C:49]([NH:54][C:13](=[O:14])[C:12]3[CH:16]=[CH:17][C:9]([N:6]4[CH2:7][CH2:8][N:3]([CH3:2])[CH2:4][CH2:5]4)=[CH:10][CH:11]=3)=[N:50][NH:51]2)=[CH:47][CH:46]=1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 7365324-(4-Methylpiperazin-1-yl)benzoic acidHCID 70982760HCID 70982760, compoundHCID 86712573HCID 86712573, compound

Product 1

HCID 70982140HCID 70982140, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

A stirred suspension of 4-(4-methyl-piperazin-1-yl)-benzoyl chloride hydrochloride, prepared from 4.55 g (20.7 mmol) of 4-(4-methyl-piperazin-1-yl)-benzoic acid as described above in preparation 3, in dry pyridine (50 ml) was treated dropwise, at 0° C., under argon atmosphere, with a solution of 6-(2-benzyloxy-ethoxy)-1H-indazol-3-ylamine (5.31 g, 18.8 mmol) in 80 ml of dry pyridine. The reaction mixture was allowed to warm to r.t. under stirring overnight, then concentrated to 30 ml by rotary evaporation, poured into 500 ml of saturated solution of NaHCO3 and extracted with 300+100 ml of DCM. The organic layers were combined, dried over sodium sulfate and evaporated to dryness. The crude residue was treated with 200 ml of EtOAc and stirred at reflux for 2 h. After cooling to r.t. the solid was filtered, washed with EtOAc and dried in oven at 50° C. under high vacuum to afford 5.23 g (yield: 57%) of the title compound as a white solid.

Workup

  1. concentrationconcentrated to 30 ml by rotary evaporation
  2. additionpoured into 500 ml of saturated solution of NaHCO3
  3. extractionextracted with 300+100 ml of DCM
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness
  6. additionThe crude residue was treated with 200 ml of EtOAc
  7. stirringstirred
  8. temperatureat reflux for 2 h
  9. temperatureAfter cooling to r.t. the solid
  10. filtrationwas filtered
  11. washwashed with EtOAc
  12. customdried in oven at 50° C. under high vacuum

Sources & evidence

ORD record
ord-fb37bb7abe794d859ff341fe2963c309
Source dataset
uspto-grants-2016_08
Patent number
US09408850B2

Reaction notes

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