Water → HCID 136381035, compound

HRID 1051779Notes

Reaction equation

HRID 1051779 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10]([C:12]#[N:13])=[N:9][C:8]([C@@H:14]([NH:16][C:17]1[N:25]=[CH:24][N:23]=[C:22]3[C:18]=1[N:19]=[CH:20][N:21]3[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1)[CH3:15])=[CH:7]2.Cl.[NH2:36][OH:37].[OH-].[Na+].O>CCO>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](/[C:12](=[N:36]/[OH:37])/[NH2:13])=[N:9][C:8]([C@@H:14]([NH:16][C:17]1[N:25]=[CH:24][N:23]=[C:22]3[C:18]=1[N:19]=[CH:20][N:21]3[CH2:26][C:27]1[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=1)[CH3:15])=[CH:7]2

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 68751216HCID 68751216, compound

Product 1

HCID 136381035HCID 136381035, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of (S)-8-chloro-3-(1-((9-(4-methoxybenzyl)-9H-purin-6-yl)amino)ethyl)isoquinoline-1-carbonitrile 29 (600 mg, 1.28 mmol, 1.0 eq), hydroxylamine hydrochloride (269 mg, 3.84 mmol, 3 eq) and NaOH (154 mg, 3.84 mmol, 3 eq) in EtOH (15 mL) was stirred at reflux 4 h. The mixture was cooled to RT, poured into water (100 mL) and then extracted with DCM (3×100 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 (1-10% MeOH-DCM) to afford the product (S,Z)-8-chloro-N′-hydroxy-3-(1-((9-(4-methoxybenzyl)-9H-purin-6-yl)amino)ethyl)isoquinoline-1-carboximidamide 30.

Workup

  1. temperatureat reflux 4 h
  2. extractionextracted with DCM (3×100 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel (1-10% MeOH-DCM)

Sources & evidence

ORD record
ord-9ff30603c79f46caa77fa8c0dfc7079b
Source dataset
uspto-grants-2016_07
Patent number
US09388183B2

Reaction notes

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