Water → HCID 68749417, compound

HRID 1396614Notes

Reaction equation

HRID 1396614 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7](=[O:14])[CH2:8][C:9](OCC)=O)[CH2:3][CH2:2]1.[H-].[Na+].ClC1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][C:26]=2[Cl:28])[CH:21]=[C:20]([C@@H:29]([NH:31][C:32]2[N:40]=[CH:39][N:38]=[C:37]3[C:33]=2[N:34]=[CH:35][N:36]3[CH2:41][C:42]2[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=2)[CH3:30])[N:19]=1.O>C1COCC1>[Cl:28][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:27]=1[C:9]([CH2:8][C:7]([N:4]1[CH2:3][CH2:2][O:1][CH2:6][CH2:5]1)=[O:14])=[N:19][C:20]([C@@H:29]([NH:31][C:32]1[N:40]=[CH:39][N:38]=[C:37]3[C:33]=1[N:34]=[CH:35][N:36]3[CH2:41][C:42]1[CH:43]=[CH:44][C:45]([O:48][CH3:49])=[CH:46][CH:47]=1)[CH3:30])=[CH:21]2

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2785816HCID 2785816, compoundHCID 86665021HCID 86665021, compound

Product 1

HCID 68749417HCID 68749417, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of ethyl 3-morpholino-3-oxopropanoate 33 (402 mg, 2 mmol, 1.0 eq) and NaH (144 mg, 3 mmol, 1.5 eq) in THF (3 mL) at RT, (S)—N-(1-(1,8-dichloroisoquinolin-3-yl)ethyl)-9-(4-methoxybenzyl)-9H-purin-6-amine 1 (765 mg, 1.6 mmol, 0.8 eq) was added and the resulting mixture was stirred at reflux overnight. The reaction mixture was poured into water (50 mL) and extracted with DCM (3×50 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 (1-5% MeOH-DCM) to afford the product (S)-2-(8-chloro-3-(1-((9-(4-methoxybenzyl)-9H-purin-6-yl)amino)ethyl)isoquinolin-1-yl)-1-morpholinoethanone 34.

Workup

  1. temperatureat reflux overnight
  2. extractionextracted with DCM (3×50 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 (1-5% MeOH-DCM)

Sources & evidence

ORD record
ord-c32d809bbdbc44da9b5d0219ab8ed1d2
Source dataset
uspto-grants-2014_12
Patent number
US08901133B2

Reaction notes

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