2-Methylindole → N,N-dimethyl-1-((2-(2-methyl-1H-indol-1-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-amine

HRID 1692872Notes

Reaction equation

HRID 1692872 reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.[H-].[Na+].Cl[C:14]1[N:15]=[C:16]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)[C:17]2[S:22][C:21]([CH2:23][N:24]3[CH2:29][CH2:28][CH:27]([N:30]([CH3:32])[CH3:31])[CH2:26][CH2:25]3)=[CH:20][C:18]=2[N:19]=1>CN(C=O)C.O>[CH3:31][N:30]([CH3:32])[CH:27]1[CH2:28][CH2:29][N:24]([CH2:23][C:21]2[S:22][C:17]3[C:16]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)=[N:15][C:14]([N:3]4[C:4]5[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=5)[CH:10]=[C:2]4[CH3:1])=[N:19][C:18]=3[CH:20]=2)[CH2:25][CH2:26]1

Participants

6

Reactant 3

HCID 72242-MethylindoleHCID 24758Sodium hydrideHCID 575067401-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amine

Product 1

HCID 49820979N,N-dimethyl-1-((2-(2-methyl-1H-indol-1-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-amineYield 12.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A solution of 2-methylindole (0.131 g) in DMF (8 mL) was cooled to 0° C. then sodium hydride (0.06 g) added. After 15 min [1-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-dimethyl-amine (0.395 g) was added. The reaction vessel was sealed and heated at 150° C. After 1 h the reaction mixture was cooled to room temperature and diluted with water. The resulting precipitate was collected by filtration then purified by chromatography (silica, 0 to 20% of a 49:1 MeOH:NH4OH mixture in dichloromethane) to furnish the title compound (0.059 g, 12%) as a light brown solid. MS m/e 491 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.33-1.57 (m, 2H) 1.74 (d, J=12.43 Hz, 2H) 2.08 (t, J=10.55 Hz, 3H) 2.18 (s, 6H) 2.64 (s, 3H) 2.95 (d, J=11.30 Hz, 2H) 3.74-3.87 (m, 6H) 3.89-4.04 (m, 4H) 6.42 (s, 1H) 6.98-7.20 (m, 2H) 7.37 (s, 1H) 7.43-7.56 (m, 1H) 8.03 (d, J=7.54 Hz, 1H)

Workup

  1. customThe reaction vessel was sealed
  2. temperatureAfter 1 h the reaction mixture was cooled to room temperature
  3. filtrationThe resulting precipitate was collected by filtration
  4. customthen purified by chromatography (silica, 0 to 20% of a 49:1 MeOH:NH4OH mixture in dichloromethane)

Sources & evidence

ORD record
ord-50772e4f52e344209b219eb05f0df787
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

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