Sodium hydride → HCID 59603511, compound

HRID 1692885Notes

Reaction equation

HRID 1692885 reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([F:11])=[CH:6][CH:5]=2.[H-].[Na+].Cl[C:15]1[N:16]=[C:17]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)[C:18]2[S:23][C:22]([CH2:24][N:25]3[CH2:30][CH2:29][CH:28]([N:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]3)=[CH:21][C:19]=2[N:20]=1>CN(C=O)C.O.[Cl-].[Na+]>[F:11][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]([C:15]1[N:16]=[C:17]([N:34]3[CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)[C:18]3[S:23][C:22]([CH2:24][N:25]4[CH2:26][CH2:27][CH:28]([N:31]([CH3:33])[CH3:32])[CH2:29][CH2:30]4)=[CH:21][C:19]=3[N:20]=1)[C:2]([CH3:1])=[CH:10]2

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 27787155-Fluoro-2-methylindoleHCID 575067401-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amine

Product 1

HCID 59603511HCID 59603511, compoundYield 10.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 5234Sodium ChlorideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A solution of 2-methyl-5-fluoroindole (0.164 g) in DMF (6 mL) was cooled to 0° C. then sodium hydride (0.066 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 resulting residual oil was separated from the aqueous layer, and then purified by chromatography (silica, 0 to 20% of a 49:1 MeOH:NH4OH mixture in dichloromethane) to furnish 119 (0.053 g, 10%) as a yellow solid. MS m/e 509 [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) 2.64 (s, 3H) 2.95 (d, 2H) 3.74-3.87 (m, 6H) 3.89-4.04 (m, 4H) 6.42 (s, 1H) 6.98-7.20 (m, 1H) 7.37 (m, 1H) 7.43 (s, 1H) 8.03 (m, 1H).

Workup

  1. customThe reaction vessel was sealed
  2. temperatureAfter 3 h the reaction mixture was cooled to room temperature
  3. customThe resulting residual oil was separated from the aqueous layer
  4. custompurified by chromatography (silica, 0 to 20% of a 49:1 MeOH:NH4OH mixture in dichloromethane)

Sources & evidence

ORD record
ord-29e011a5c3bf4260bdd8fb4c3d0668f5
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

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