6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine → tert-Butyl 4-[3-chloro-6-methoxy-2-methyl-5-(1-{[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]amino}ethyl)phenyl]piperidine-1-carboxylate

HRID 510967Notes

Reaction equation

HRID 510967 reaction equation
[NH2:1][CH:2]([C:4]1[C:5]([O:25][CH3:26])=[C:6]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)[C:7]([CH3:11])=[C:8]([Cl:10])[CH:9]=1)[CH3:3].Cl[C:28]1[N:36]=[CH:35][N:34]=[C:33]2[C:29]=1[N:30]=[CH:31][N:32]2[CH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][O:38]1.C(=O)(O)[O-].[Na+]>C(O)CCC>[Cl:10][C:8]1[C:7]([CH3:11])=[C:6]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:14][CH2:13]2)[C:5]([O:25][CH3:26])=[C:4]([CH:2]([NH:1][C:28]2[N:36]=[CH:35][N:34]=[C:33]3[C:29]=2[N:30]=[CH:31][N:32]3[CH:37]2[CH2:42][CH2:41][CH2:40][CH2:39][O:38]2)[CH3:3])[CH:9]=1

Participants

5

Reactant 3

HCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 516892Sodium BicarbonateHCID 86666879Tert-butyl 4-{3-[1-aminoethyl]-5-chloro-2-methoxy-6-methylphenyl}piperidine-1-carboxylate

Product 1

HCID 86666880tert-Butyl 4-[3-chloro-6-methoxy-2-methyl-5-(1-{[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]amino}ethyl)phenyl]piperidine-1-carboxylateYield 109%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of tert-butyl 4-{3-[1-aminoethyl]-5-chloro-2-methoxy-6-methylphenyl}piperidine-1-carboxylate (150 mg, 0.392 mmol), 6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (122 mg, 0.509 mmol), and sodium bicarbonate (35 mg, 0.41 mmol) in 1-butanol (4.7 mL) was degassed with N2 for ˜5 minutes. The mixture was heated at 110° C. for 3 h under nitrogen. The solvent was removed under reduced pressure and the resulting residue was diluted with EtOAc, washed with sat. NaHCO3, water, brine, dried over Na2SO4, filtered and concentrated. The residue was purified by chromatography eluting with 0 to 80% EtOAc in CH2Cl2 to provide the desired product (0.25 g). LCMS calculated for C30H42ClN6O4 (M+H)+: m/z=585.3. found: =585.3.

Workup

  1. customwas degassed with N2 for ˜5 minutes
  2. customThe solvent was removed under reduced pressure
  3. additionthe resulting residue was diluted with EtOAc
  4. washwashed with sat. NaHCO3, water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography
  9. washeluting with 0 to 80% EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-146b50aea01d40459055e915bf37592a
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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