Diisopropylethylamine → N-[1-(3-Bromo-5-chloro-2-methoxyphenyl)ethyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 510918Notes

Reaction equation

HRID 510918 reaction equation
[Br:1][C:2]1[C:3]([O:12][CH3:13])=[C:4]([CH:9]([NH2:11])[CH3:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.Br[C:15]1[N:23]=[CH:22][N:21]=[C:20]2[C:16]=1[N:17]=[CH:18][N:19]2[CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][O:25]1.C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].[Na+]>C(O)C>[Br:1][C:2]1[C:3]([O:12][CH3:13])=[C:4]([CH:9]([NH:11][C:15]2[N:23]=[CH:22][N:21]=[C:20]3[C:16]=2[N:17]=[CH:18][N:19]3[CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)[CH3:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 162280251-(3-Bromo-5-chloro-2-methoxyphenyl)ethanamineHCID 583686166-Bromo-9-(tetrahydro-2H-pyran-2-YL)-9H-purine

Product 1

HCID 67969174N-[1-(3-Bromo-5-chloro-2-methoxyphenyl)ethyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amineYield 98.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 1-(3-bromo-5-chloro-2-methoxyphenyl)ethanamine (2.2 g, 8.5 mmol) in ethanol (69 mL), was treated with 6-bromo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (3.6 g, 13 mmol, from Example 108, Step 1) and N,N-diisopropylethylamine (4.4 mL, 25 mmol) and heated at reflux overnight. The reaction mixture was cooled, poured into sodium bicarbonate (150 mL) and extracted with ethyl acetate (2×150 mL). The combined organic layers were washed with water and brine, dried with sodium sulfate, filtered, and concentrated to a crude residue. Purification by flash column chromatography using acetonitrile in dichloromethane (5%-10%) and then ethyl acetate in hexanes (60%-100%) gave the desired product (3.9 g, 98%). LCMS for C19H22BrClN5O2 (M+H)+: m/z=466.1, 468.1. Found: 466.0, 468.0.

Workup

  1. temperatureheated
  2. temperatureat reflux overnight
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted with ethyl acetate (2×150 mL)
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to a crude residue
  9. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-ed99a6b731764d5d89ad73fc2d515fc3
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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