5-Benzyloxyindole → HCID 59603424, compound

HRID 1692892Notes

Reaction equation

HRID 1692892 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[CH:12]2)C1C=CC=CC=1.[H-].[Na+].Cl[C:21]1[N:22]=[C:23]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[C:24]2[S:29][C:28]([CH2:30][N:31]3[CH2:36][CH2:35][CH:34]([N:37]([CH3:39])[CH3:38])[CH2:33][CH2:32]3)=[CH:27][C:25]=2[N:26]=1>CN(C=O)C.O.[Cl-].[Na+].C(O)C.ClCCl.[Pd]>[CH3:38][N:37]([CH3:39])[CH:34]1[CH2:35][CH2:36][N:31]([CH2:30][C:28]2[S:29][C:24]3[C:23]([N:40]4[CH2:45][CH2:44][O:43][CH2:42][CH2:41]4)=[N:22][C:21]([N:14]4[C:15]5[C:11](=[CH:10][C:9]([OH:8])=[CH:17][CH:16]=5)[CH:12]=[CH:13]4)=[N:26][C:25]=3[CH:27]=2)[CH2:32][CH2:33]1

Participants

10

Reactant 3

HCID 146245-BenzyloxyindoleHCID 24758Sodium hydrideHCID 575067401-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amine

Product 1

HCID 59603424HCID 59603424, compoundYield 15%

Reagents, catalysts & solvents 6

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 5234Sodium ChlorideSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

A solution of 5-benzyloxyindole (0.245 g) in DMF (5 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 1 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). The residue obtained was dissolved in ethanol (30 mL) and dichloromethane (20 mL). Palladium on carbon (10%, 40 mg) was added. The mixture was degassed and was purged with hydrogen, and continued under a hydrogen balloon overnight. The reaction mixture was filtered through solka floc. The filtrate was concentrated and purified by chromatography (silica, 0 to 20% of a 49:1 MeOH:NH4OH mixture in dichloromethane) to furnish 132 (0.012 g, 15%) as a white solid. MS m/e 493 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.7-1.8 (m, 2H), 2.0-2.1 (d, 2H), 2.3 (m, 3H), 2.7 (s, 6H), 2.95 (d, 2H), 3.2 (m, 2H), 3.89-4.04 (m, 10H), 6.5 (d, 1H), 6.75 (d, 1H), 6.95 (d, 1H), 7.2 (br. s, 1H), 7.4 (s, 1H), 8.2 (d, 1H), 8.5 (d, 1H).

Workup

  1. customThe reaction vessel was sealed
  2. temperatureAfter 1 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)
  6. customThe residue obtained
  7. customThe mixture was degassed
  8. customwas purged with hydrogen
  9. customballoon overnight
  10. filtrationThe reaction mixture was filtered through solka floc
  11. concentrationThe filtrate was concentrated
  12. custompurified by chromatography (silica, 0 to 20% of a 49:1 MeOH:NH4OH mixture in dichloromethane)

Sources & evidence

ORD record
ord-1488c58043c7469a8ada97c0b6b6640a
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

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