Triethylamine → 6-[(S)-4-(4-Chloro-phthalazin-1-yl)-3-methyl-piperazin-1-yl]-nicotinic acid ethyl ester

HRID 42206

Reaction equation

HRID 42206 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][NH:14][C@@H:13]([CH3:17])[CH2:12]2)=[N:7][CH:6]=1)[CH3:2].[Cl:19][C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](Cl)=[N:22][N:21]=1.C(N(CC)CC)C>CN1C(=O)CCC1.O>[CH2:1]([O:3][C:4](=[O:18])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][N:14]([C:23]3[C:24]4[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:20]([Cl:19])=[N:21][N:22]=3)[C@@H:13]([CH3:17])[CH2:12]2)=[N:7][CH:6]=1)[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 784901,4-DichlorophthalazineHCID 574716156-((S)-3-Methyl-piperazin-1-yl)-nicotinic acid ethyl ester

Product 1

HCID 592406816-[(S)-4-(4-Chloro-phthalazin-1-yl)-3-methyl-piperazin-1-yl]-nicotinic acid ethyl esterYield 30.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 6-((S)-3-methyl-piperazin-1-yl)-nicotinic acid ethyl ester (1.0 g, 4.0 mmol, 1 eq), 1,4-dichlorophthalazine (840 mg, 4.2 mmol, 1.05 eq) and triethyl amine (3.9 g, 2.8 mL, 38 mmol, 9.5 eq) in NMP (8 mL) is heated at 100 C for 26 h. Reaction is diluted with water (15 mL) and extracted with EtOAc (3×25 mL). The combined organic fractions are dried over magnesium sulfate, concentrated and purified by silica gel chromatography (5-50% EtOAc/Heptane) to yield the desired compound (500 mg, 30% yield).

Workup

  1. customReaction
  2. extractionextracted with EtOAc (3×25 mL)
  3. dry with materialThe combined organic fractions are dried over magnesium sulfate
  4. concentrationconcentrated
  5. custompurified by silica gel chromatography (5-50% EtOAc/Heptane)

Sources & evidence

ORD record
ord-982eee3b37a14de48eded3e20b948774
Source dataset
uspto-grants-2013_09
Patent number
US08536168B2

Linked notes

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