Diisopropylethylamine → HCID 178423767, compound

HRID 1506109Notes

Reaction equation

HRID 1506109 reaction equation
[NH2:1][C@H:2]([C:4]1[N:5]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:6](=[O:15])[C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][C:8]=2[CH3:14])[CH3:3].[NH2:22][C:23]1[N:31]=[C:30]2[C:26]([NH:27][CH:28]=[N:29]2)=[C:25](Cl)[N:24]=1.C(N(CC)C(C)C)(C)C>CCCCO>[NH2:22][C:23]1[N:31]=[C:30]2[C:26]([N:27]=[CH:28][NH:29]2)=[C:25]([NH:1][C@H:2]([C:4]2[N:5]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:6](=[O:15])[C:7]3[C:12]([CH:13]=2)=[CH:11][CH:10]=[CH:9][C:8]=3[CH3:14])[CH3:3])[N:24]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 53603492-Amino-6-chloropurine2×HCID 58008747(S)-3-(1-aminoethyl)-8-methyl-2-phenylisoquinolin-1(2H)-one2×

Product 1

HCID 178423767HCID 178423767, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

(S)-3-(1-Aminoethyl)-8-methyl-2-phenylisoquinolin-1(2H)-one (compound 4704) (100 mg, 0.36 mmol), 2-Amino-6-chloropurine (compound 5401) (60.9 mg, 0.36 mmol) and N,N-diisopropylethyl amine (69 μL, 0.40 mmol) were suspended in n-BuOH (4 mL) in a sealed tube, and the resulting mixture was stirred at 100° C. for 48 h and then at 120° C. for 24 h. The mixture was allowed to cool to room temperature and concentrate in vacuo to remove n-BuOH. The residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo. The residue was triturated with anhydrous ethyl ether and further purified by flash column chromatography on silica gel (eluting with 0-8% MeOH/DCM) to afford the desired product, (S)-3-(1-(2-amino-9H-purin-6-ylamino)ethyl)-8-methyl-2-phenylisoquinolin-1(2H)-one as a off white/yellow solid (compound 5402), (28 mg, 20%).

Workup

  1. waitat 120° C. for 24 h
  2. temperatureto cool to room temperature
  3. concentrationconcentrate in vacuo
  4. customto remove n-BuOH
  5. customThe residue was partitioned between ethyl acetate and water
  6. washThe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customThe residue was triturated with anhydrous ethyl ether
  11. customfurther purified by flash column chromatography on silica gel (eluting with 0-8% MeOH/DCM)

Sources & evidence

ORD record
ord-723f9e007f404a2f957b6ae5f550f553
Source dataset
uspto-grants-2015_12
Patent number
US09216982B2

Reaction notes

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