Diisopropylethylamine → 2-cyclopropyl-8-methyl-3-((1S)-1-(9-(tetrahydro-2H-Pyran-2-yl)-9H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one

HRID 1506103Notes

Reaction equation

HRID 1506103 reaction equation
N[C@H](C1N(C2CC2)C(=O)C2C(C=1)=CC=CC=2C)C.ClC1N=CN=C2C=1N=CN2C1CCCCO1.CCN(C(C)C)C(C)C.[CH:44]1([N:47]2[C:56]([C@@H:57]([NH:59][C:60]3[N:68]=[CH:67][N:66]=[C:65]4[C:61]=3[N:62]=[CH:63][N:64]4[CH:69]3[CH2:74][CH2:73][CH2:72][CH2:71][O:70]3)[CH3:58])=[CH:55][C:54]3[C:49](=[C:50]([CH3:75])[CH:51]=[CH:52][CH:53]=3)[C:48]2=[O:76])[CH2:46][CH2:45]1>CCCCO>[N:68]1[C:60]([NH:59][C@H:57]([C:56]2[N:47]([CH:44]3[CH2:46][CH2:45]3)[C:48](=[O:76])[C:49]3[C:54]([CH:55]=2)=[CH:53][CH:52]=[CH:51][C:50]=3[CH3:75])[CH3:58])=[C:61]2[C:65]([NH:64][CH:63]=[N:62]2)=[N:66][CH:67]=1.[CH:44]1([N:47]2[C:56]([C@@H:57]([NH:59][C:60]3[N:68]=[CH:67][N:66]=[C:65]4[C:61]=3[N:62]=[CH:63][N:64]4[CH:69]3[CH2:74][CH2:73][CH2:72][CH2:71][O:70]3)[CH3:58])=[CH:55][C:54]3[C:49](=[C:50]([CH3:75])[CH:51]=[CH:52][CH:53]=3)[C:48]2=[O:76])[CH2:45][CH2:46]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 58008913(S)-3-(1-Aminoethyl)-2-cyclopropyl-8-methylisoquinolin-1(2H)-one2×HCID 580089832-cyclopropyl-8-methyl-3-((1S)-1-(9-(tetrahydro-2H-Pyran-2-yl)-9H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one

Product 2

HCID 580089832-cyclopropyl-8-methyl-3-((1S)-1-(9-(tetrahydro-2H-Pyran-2-yl)-9H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-oneYield 65%HCID 178423765(S)-3-(1-(9H-purin-6-ylamino)ethyl)-2-cyclopropyl-8-methylisoquinolin-1(2H)-one

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

(S)-3-(1-Aminoethyl)-2-cyclopropyl-8-methylisoquinolin-1(2H)-one (242 mg, 1 mmol) (compound 5003), 6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (344 mg, 1.44 mmol) and DIPEA (279 mg, 2.16 mmol) were dissolved in n-BuOH (20 mL), and the resulting mixture was stirred at reflux for 16 h. The reaction mixture was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (eluting with 30% to 50% Hex/EA) to afford the desired product, 2-cyclopropyl-8-methyl-3-((1S)-1-(9-(tetrahydro-2H-Pyran-2-yl)-9H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one (compound 5004) (288 mg, 65% yield) as a white solid.

Workup

  1. temperatureat reflux for 16 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue was purified by flash column chromatography on silica gel (eluting with 30% to 50% Hex/EA)

Sources & evidence

ORD record
ord-8b3d6faba2fc4b9aa702ee0a6e146347
Source dataset
uspto-grants-2015_12
Patent number
US09216982B2

Reaction notes

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