Diisopropylethylamine → (3R)-3-[(2-Chloro-benzoyl)amino]-N-methyl-N-[1-(2-methylamino-pyrimidin-4-yl)-piperidin-4-yl]-2,3-dihydro-1H-indene-5-carboxylic acid amide

HRID 1193425Notes

Reaction equation

HRID 1193425 reaction equation
[Cl:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[C:4]([NH:6][C@H:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([N:18]([CH3:25])[CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[O:17])[CH:14]=2)[CH2:9][CH2:8]1)=[O:5].Cl[C:31]1[CH:36]=[CH:35][N:34]=[C:33](CN)[N:32]=1.C[CH2:40][N:41](C(C)C)C(C)C>O1CCOCC1>[Cl:1][C:2]1[CH:29]=[CH:28][CH:27]=[CH:26][C:3]=1[C:4]([NH:6][C@H:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([N:18]([CH3:25])[CH:19]3[CH2:20][CH2:21][N:22]([C:35]4[CH:36]=[CH:31][N:32]=[C:33]([NH:41][CH3:40])[N:34]=4)[CH2:23][CH2:24]3)=[O:17])[CH:14]=2)[CH2:9][CH2:8]1)=[O:5]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 22460689(4-Chloropyrimidin-2-YL)methanamineHCID 66798745(R)-3-(2-chlorobenzamido)-N-methyl-N-(piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide

Product 1

HCID 66798485(3R)-3-[(2-Chloro-benzoyl)amino]-N-methyl-N-[1-(2-methylamino-pyrimidin-4-yl)-piperidin-4-yl]-2,3-dihydro-1H-indene-5-carboxylic acid amideYield 49%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of (R)-3-(2-chlorobenzamido)-N-methyl-N-(piperidin-4-yl)-2,3-dihydro-1H-indene-5-carboxamide (400 mg, 0.973 mmol, 1 eq), (4-chloropyrimidin-2-yl)methylamine (280 mg, 1.946 mmol, 2 eq) and DIPEA (0.33 ml, 1.946 mmol, 2 eq) in dioxane (10 ml) was refluxed for 16 h. When the reaction was complete according to TLC monitoring, concentration under reduced pressure was carried out and the residue was taken up in dichloromethane (100 ml) and washed with water (40 ml) and saturated sodium chloride solution (40 ml). The organic phase was dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 6% methanol in dichloromethane). The desired product was in the form of a white solid. Yield: 49% (250 mg, 0.482 mmol)

Workup

  1. temperaturewas refluxed for 16 h
  2. concentrationWhen the reaction was complete according to TLC monitoring, concentration under reduced pressure
  3. washwashed with water (40 ml) and saturated sodium chloride solution (40 ml)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography (silica gel, 6% methanol in dichloromethane)

Sources & evidence

ORD record
ord-6bcc00b5450949dc97599b25f3778581
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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