Sodium hydride → 1-((2-(5-fluoro-1H-indol-1-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amine

HRID 1692886Notes

Reaction equation

HRID 1692886 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH: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.[Cl-].[Na+]>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:14]1[N:15]=[C:16]([N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)[C:17]3[S:22][C:21]([CH2:23][N:24]4[CH2:25][CH2:26][CH:27]([N:30]([CH3:32])[CH3:31])[CH2:28][CH2:29]4)=[CH:20][C:18]=3[N:19]=1)[CH:6]=[CH:5]2

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 678615-FluoroindoleHCID 575067401-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amine

Product 1

HCID 596035191-((2-(5-fluoro-1H-indol-1-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amineYield 51.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 5234Sodium ChlorideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A solution of 5-fluoroindole (0.148 g) in DMF (6 mL) was cooled to 0° C. then sodium hydride (0.06 g) added. After 30 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 3 h the reaction mixture was cooled to room temperature and diluted with water and saturated aqueous sodium chloride solution. The solid separated was filtered, and then purified by chromatography (silica, 0 to 20% of a 49:1 MeOH:NH4OH mixture in dichloromethane) to furnish 120 (0.252 g, 51%) as a off white solid. MS m/e 495 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.33-1.57 (m, 2H) 1.74 (d, 2H) 2.08 (t, 3H) 2.18 (s, 6H) 2.95 (d, 2H) 3.74-3.87 (m, 6H) 3.89-4.04 (m, 4H) 6.75 (d, 1H) 7.0-7.10 (m, 1H) 7.37 (s, 1H) 7.6-7.7 (m, 1H) 8.33 (d, 1H) 8.5-8.6 (d, 1H).

Workup

  1. customThe reaction vessel was sealed
  2. temperatureAfter 3 h the reaction mixture was cooled to room temperature
  3. customThe solid separated
  4. filtrationwas filtered
  5. custompurified by chromatography (silica, 0 to 20% of a 49:1 MeOH:NH4OH mixture in dichloromethane)

Sources & evidence

ORD record
ord-387f5086faf64cb1beec033cd9ca60b7
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

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