Triethylamine → 8-Chloro-2-phenyl-3-[(1S)-1-[[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]amino]ethyl]-1(2H)-isoquinolinone

HRID 928539Notes

Reaction equation

HRID 928539 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[Cl:14])[CH3:3].Cl[C:23]1[N:31]=[CH:30][N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][N:27]2[CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][O:33]1.C(N(CC)CC)C>C(O)(C)C>[Cl:14][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:7]=1[C:6](=[O:15])[N:5]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:4]([C@@H:2]([NH:1][C:23]1[N:31]=[CH:30][N:29]=[C:28]3[C:24]=1[N:25]=[CH:26][N:27]3[CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][O:33]1)[CH3:3])=[CH:13]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine2×HCID 66607319(S)-3-(1-aminoethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one2×

Product 1

HCID 666077098-Chloro-2-phenyl-3-[(1S)-1-[[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]amino]ethyl]-1(2H)-isoquinolinone

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
82 °C

Procedure

3-(1-Aminoethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one (Compound 9) and 6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (Compound 4) are combined in the presence of triethylamine and isopropyl alcohol. The reaction solution is heated at 82° C. for 24 hours to afford Compound 10. The intermediate compound 10 is treated with concentrated HCl and ethanol under aqueous conditions at 35° C. to remove the tetrahydropyranyl group to yield (S)-3-(1-(9H-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one. Isolation/purification under aqueous conditions affords polymorph Form C.

Sources & evidence

ORD record
ord-7bd8ae8202de40f8a7d2befe75168ac3
Source dataset
uspto-grants-2016_03
Patent number
US09290497B2

Reaction notes

Loading…