Water → HCID 178474885, compound

HRID 1396615Notes

Reaction equation

HRID 1396615 reaction equation
[OH:1][CH2:2][CH2:3][NH:4][C:5](=[O:7])[CH3:6].[H-].[Na+].Cl[C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][C:19]=2[Cl:21])[CH:14]=[C:13]([C@@H:22]([NH:24][C:25]2[N:33]=[CH:32][N:31]=[C:30]3[C:26]=2[N:27]=[CH:28][N:29]3C(OC(C)(C)C)=O)[CH3:23])[N:12]=1.O>C1COCC1>[N:33]1[C:25]([NH:24][C@H:22]([C:13]2[N:12]=[C:11]([O:1][CH2:2][CH2:3][NH:4][C:5](=[O:7])[CH3:6])[C:20]3[C:15]([CH:14]=2)=[CH:16][CH:17]=[CH:18][C:19]=3[Cl:21])[CH3:23])=[C:26]2[C:30]([NH:29][CH:28]=[N:27]2)=[N:31][CH:32]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8880AcetylethanolamineHCID 24758Sodium hydrideHCID 86665025HCID 86665025, compound

Product 1

HCID 178474885HCID 178474885, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of N-(2-hydroxyethyl)acetamide (110 mg, 1.07 mmol, 2.43 eq) in THF (20 mL) at 0° C., NaH (60% in mineral oil, 110 mg, 2.75 mmol, 6.25 eq) was added and the resulting mixture was stirred for 15 min. To this mixture, (S)-tert-butyl 6-(1-(1,8-dichloroisoquinolin-3-yl)ethylamino)-9H-purine-9-carboxylate 39 (200 mg, 0.44 mmol, 1.0 eq) was added. The resulting mixture was stirred at reflux for 2 h, cooled to RT and then poured into water (30 mL). The mixture was extracted with DCM (3×30 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 (3% MeOH-DCM) to afford the product (S)—N-(2-(3-(1-(9H-purin-6-ylamino)ethyl)-8-chloroisoquinolin-1-yloxy)ethyl)acetamide 40. ESI-MS m/z: 426.0 [M+H]+.

Workup

  1. stirringThe resulting mixture was stirred
  2. temperatureat reflux for 2 h
  3. extractionThe mixture was extracted with DCM (3×30 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by flash column chromatography on silica gel (3% MeOH-DCM)

Sources & evidence

ORD record
ord-a2928e02b3de43a79bfb10ede40ee648
Source dataset
uspto-grants-2014_12
Patent number
US08901133B2

Reaction notes

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