Water → HCID 178456301, compound

HRID 1396618Notes

Reaction equation

HRID 1396618 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[H-].[Na+].Cl[C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][C:22]=2[Cl:24])[CH:17]=[C:16]([C@@H:25]([NH:27][C:28]2[N:36]=[CH:35][N:34]=[C:33]3[C:29]=2[N:30]=[CH:31][NH:32]3)[CH3:26])[N:15]=1.O>C1COCC1>[Cl:24][C:22]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:23]=1[C:14]([O:10][CH:7]1[CH2:8][CH2:9][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]1)=[N:15][C:16]([C@@H:25]([NH:27][C:28]1[N:36]=[CH:35][N:34]=[C:33]3[C:29]=1[N:30]=[CH:31][NH:32]3)[CH3:26])=[CH:17]2

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 796811-Isopropylpiperidin-4-olHCID 178461880HCID 178461880, compound

Product 1

HCID 178456301HCID 178456301, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of 1-isopropylpiperidin-4-ol (120 mg, 0.83 mmol, 1.2 eq) in THF (10 mL) at 0° C., NaH (60% in mineral oil, 33.2 mg, 0.83 mmol, 1.2 eq) was added and the resulting mixture was stirred for 10 min. To this mixture, (S)—N-(1-(1,8-dichloroisoquinolin-3-yl)ethyl)-9H-purin-6-amine 38 (250 mg, 0.70 mmol, 1.0 eq) was added. The resulting mixture was stirred at reflux overnight, cooled to RT and then poured into water (20 mL). The mixture was extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (5% MeOH-DCM) to afford the product, (S)—N-(1-(8-chloro-1-(1-isopropylpiperidin-4-yloxy)isoquinolin-3-yl)ethyl)-9H-purin-6-amine 47. ESI-MS m/z: 466.2 [M+H]+.

Workup

  1. stirringThe resulting mixture was stirred
  2. temperatureat reflux overnight
  3. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by flash column chromatography on silica gel (5% MeOH-DCM)

Sources & evidence

ORD record
ord-93297c344b8e4265a2c2e3af03cdbd89
Source dataset
uspto-grants-2014_12
Patent number
US08901133B2

Reaction notes

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