Water → HCID 68749417, compound

HRID 1051782Notes

Reaction equation

HRID 1051782 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-ce59ce854c034c20a432acb2f8c69058
Source dataset
uspto-grants-2016_07
Patent number
US09388183B2

Reaction notes

Loading…