Diisopropylethylamine → 2-{6-(4-Chloro-benzyl)-2-[1-(6-methyl-pyrimidin-4-yl)-piperidin-4-ylamino]-pyrimidin-4-yl}-propan-2-ol

HRID 451415Notes

Reaction equation

HRID 451415 reaction equation
Cl.Cl.[CH3:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]([N:10]2[CH2:15][CH2:14][CH:13]([NH2:16])[CH2:12][CH2:11]2)[CH:5]=1.C(N(CC)C(C)C)(C)C.Cl[C:27]1[N:32]=[C:31]([C:33]([OH:36])([CH3:35])[CH3:34])[CH:30]=[C:29]([CH2:37][C:38]2[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=2)[N:28]=1>CN1CCCC1=O.O1CCOCC1.O>[Cl:44][C:41]1[CH:42]=[CH:43][C:38]([CH2:37][C:29]2[N:28]=[C:27]([NH:16][CH:13]3[CH2:14][CH2:15][N:10]([C:6]4[CH:5]=[C:4]([CH3:3])[N:9]=[CH:8][N:7]=4)[CH2:11][CH2:12]3)[N:32]=[C:31]([C:33]([OH:36])([CH3:35])[CH3:34])[CH:30]=2)=[CH:39][CH:40]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 673421331-(6-Methylpyrimidin-4-yl)piperidin-4-amine dihydrochlorideHCID 866567012-[2-Chloro-6-(4-chloro-benzyl)-pyrimidin-4-yl]-propan-2-ol

Product 1

HCID 533533392-{6-(4-Chloro-benzyl)-2-[1-(6-methyl-pyrimidin-4-yl)-piperidin-4-ylamino]-pyrimidin-4-yl}-propan-2-ol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of 1-(6-methyl-pyrimidin-4-yl)-piperidin-4-ylamine dihydrochloride (53 mg, 0.2 mmol) and N,N-diisopropylethyl amine (120 L, 0.7 mmol) in N-methyl-pyrrolidinone (0.5 mL) was added a solution of 2-[2-chloro-6-(4-chloro-benzyl)-pyrimidin-4-yl]-propan-2-ol (65.4 mg, 0.22 mmol)) in dioxane (1.5 mL). The reaction was heated at 160° C. in a microwave oven for 5 hours. The reaction was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a gradient from AcOEt to AcOEt/EtOH 9:1 (v/v) as eluent. The title compound was obtained as a white solid (27 mg, 30%).

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe combined organic layers were washed with water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel using a gradient from AcOEt to AcOEt/EtOH 9:1 (v/v) as eluent

Sources & evidence

ORD record
ord-649f495cb4e046c3b1dc68efbc5e8599
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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