Triethylamine → 4-Methyl-piperazine-1-carboxylic acid[2-((r)-indan-1-ylamino)-quinolin-5-yl]-amide

HRID 1671566Notes

Reaction equation

HRID 1671566 reaction equation
[C@H:1]1([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:17]([NH2:21])=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.ClC(Cl)(O[C:33](=[O:39])OC(Cl)(Cl)Cl)Cl.[CH3:41][N:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1>C1COCC1>[C@H:1]1([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[NH:21][C:33]([N:45]3[CH2:46][CH2:47][N:42]([CH3:41])[CH2:43][CH2:44]3)=[O:39])[N:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 531671-MethylpiperazineHCID 94429TriphosgeneHCID 44219082(R)-N2-Indan-1-yl-quinoline-2,5-diamine

Product 1

HCID 442195514-Methyl-piperazine-1-carboxylic acid[2-((r)-indan-1-ylamino)-quinolin-5-yl]-amideYield 32.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of (R)—N2-indan-1-yl-quinoline-2,5-diamine (example 16) (138 mg, 0.5 mmol) in THF (10 ml) was added at 0° C. triethylamine (56 mg, 0.55 mmol) and triphosgen (66.7 mg, 0.23 mmol). The white suspension was heated under reflux conditions for 3 h and triethylamine (56 mg, 0.55 mmol) and 1-methylpiperazine (55 mg, 0.55 mmol) were added at room temperature. The reaction mixture was allowed to stir at 50° C. for 16 h and was extracted with dichloromethane (2×30 ml). The combined organic layers were washed with water (2×20 ml), dried (MgSO4) and evaporated. The crude product was further purified by flash chromatography on silica gel (dichloromethane/MeOH) and crystallization (diethyl ether/heptane) to yield the title compound as off-white solid (30 mg, 15%). M.p. 142° C.; MS: m/e=402.5 (M+H+)

Workup

  1. temperatureThe white suspension was heated under reflux conditions for 3 h
  2. extractionwas extracted with dichloromethane (2×30 ml)
  3. washThe combined organic layers were washed with water (2×20 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe crude product was further purified by flash chromatography on silica gel (dichloromethane/MeOH) and crystallization (diethyl ether/heptane)

Sources & evidence

ORD record
ord-41fbea46e1204f8ba594d6ac11f71493
Source dataset
uspto-grants-2011_08
Patent number
US07994324B2

Reaction notes

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