1-Hydroxybenzotriazole → 8-(1-Chloro-6,7-dimethoxy-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione hydrochloride

HRID 900718Notes

Reaction equation

HRID 900718 reaction equation
Cl.CN(C)CCCN=C=NCC.[NH2:13][C:14]1[C:15](=[O:27])[N:16]([CH3:26])[C:17](=[O:25])[N:18]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:19]=1[NH2:20].[Cl:28][C:29]1[C:38]2[C:33](=[CH:34][C:35]([O:41][CH3:42])=[C:36]([O:39][CH3:40])[CH:37]=2)[C:32]([CH2:43][C:44](O)=O)=[CH:31][N:30]=1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl.O>[ClH:28].[Cl:28][C:29]1[C:38]2[C:33](=[CH:34][C:35]([O:41][CH3:42])=[C:36]([O:39][CH3:40])[CH:37]=2)[C:32]([CH2:43][C:44]2[NH:13][C:14]3[C:15](=[O:27])[N:16]([CH3:26])[C:17](=[O:25])[N:18]([CH2:21][CH:22]([CH3:23])[CH3:24])[C:19]=3[N:20]=2)=[CH:31][N:30]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 41103394,5-Diamino-3-isobutyl-1-methylpyrimidine-2,6-dioneHCID 22226493(1-Chloro-6,7-dimethoxy-isoquinolin-4-yl)-acetic acid

Product 1

HCID 865884638-(1-Chloro-6,7-dimethoxy-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione hydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.6M aqueous solution, 0.33 ml, 1.85 mmol) is added to a suspension of 5,6-diamino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione (0.327 g, 1.54 mmol), (1-chloro-6,7-dimethoxy-isoquinolin-4-yl)-acetic acid (0.414 g, 1.54 mmol) and 1-hydroxybenzotriazole (0.251 g, 1.85 mmol) in CH2Cl2 (2 ml). Water (2 ml) is added, the biphasic mixture is shaken for 18 hours and the the resultant solid is collected by filtration. This intermediate is suspended in methanol (10 ml), 4M aqueous NaOH (5 ml) is added and the mixture heated to reflux for 4 hours. After evaporation of the methanol, the residue is acidified to pH2 with concentrated hydrochloric acid and the resultant solid collected by filtration and purified by preparative HPLC to afford 8(1-chloro-6,7-dimethoxy-isoquinolin-4-ylmethyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione hydrochloride, [M]+ 458.

Workup

  1. filtrationthe the resultant solid is collected by filtration
  2. addition4M aqueous NaOH (5 ml) is added
  3. temperaturethe mixture heated
  4. temperatureto reflux for 4 hours
  5. customAfter evaporation of the methanol
  6. filtrationthe resultant solid collected by filtration
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-1f55169063c1423e9d6d04793139c5fe
Source dataset
uspto-grants-2008_04
Patent number
US07361661B2

Reaction notes

Loading…