Diisopropylethylamine → 6-(6-Chloro-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amide

HRID 1094528Notes

Reaction equation

HRID 1094528 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[C:15]([C:19](Cl)=[O:20])=[CH:14][CH:13]=[CH:12]3)[CH:3]=1.[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([NH2:36])=[CH:32][CH:31]=2)[CH2:25][CH2:24]1.C(N(C(C)C)CC)(C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([NH:36][C:19]([C:15]3[C:16]4[C:11](=[CH:10][C:9]([O:8][C:4]5[CH:3]=[C:2]([Cl:1])[N:7]=[CH:6][N:5]=5)=[CH:18][CH:17]=4)[CH:12]=[CH:13][CH:14]=3)=[O:20])=[CH:32][CH:31]=2)[CH2:25][CH2:24]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 31539964-((4-Methylpiperazin-1-yl)methyl)anilineHCID 574551736-(6-Chloropyrimidin-4-yloxy)naphthalene-1-carbonyl chloride

Product 1

HCID 866386246-(6-Chloro-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 2.2 mMol 6-(6-chloropyrimidin-4-yloxy)-naphthalene-1-carbonyl chloride (Step 19.3) in 15 ml CH2Cl2 is added to a stirred solution of 410 mg (2.0 mMol) 4-(4-methyl-piperazin-1-ylmethyl)-phenylamine and 680 μl (4.0 mMol) diisopropylethylamine in 15 ml CH2Cl2. After 30 min, the reaction mixture is poured into a mixture of NaHCO3 and CH2Cl2. The aq. phase is separated off and extracted with CH2Cl2. The combined organic layers are washed with water and brine, dried (Na2SO4) and concentrated to give the crude product which is purified by column chromatography (SiO2; CH2Cl2/EtOH/NH3 95:4.5:0.5) to afford the title compound as a yellow powder.

Workup

  1. customThe aq. phase is separated off
  2. extractionextracted with CH2Cl2
  3. washThe combined organic layers are washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customto give the crude product which
  7. customis purified by column chromatography (SiO2; CH2Cl2/EtOH/NH3 95:4.5:0.5)

Sources & evidence

ORD record
ord-6ec50ca45a6c414b842759d61c0cb831
Source dataset
uspto-grants-2012_03
Patent number
US08133886B2

Reaction notes

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