Sodium Hydroxide → 2-methoxy-4-(2-{4-[2-(3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl)ethyl]piperazin-1-yl}ethyl)benzonitrile

HRID 1519625Notes

Reaction equation

HRID 1519625 reaction equation
Cl.[CH3:2][CH:3]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH2:13][CH2:14][N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[CH:10]=2)[C:5](=[O:21])[O:4]1.[OH-].[Na+].[CH3:24][O:25][C:26]1[CH:33]=[C:32]([CH2:34][CH:35]=O)[CH:31]=[CH:30][C:27]=1[C:28]#[N:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CCO>[CH3:24][O:25][C:26]1[CH:33]=[C:32]([CH2:34][CH2:35][N:18]2[CH2:17][CH2:16][N:15]([CH2:14][CH2:13][C:9]3[CH:10]=[C:11]4[C:6](=[CH:7][CH:8]=3)[C:5](=[O:21])[O:4][CH:3]([CH3:2])[CH2:12]4)[CH2:20][CH2:19]2)[CH:31]=[CH:30][C:27]=1[C:28]#[N:29]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 675156493-methyl-6-[2-(piperazin-1-yl)ethyl]-3,4-dihydro-1H-isochromen-1-one hydrochlorideHCID 772312592-(Methyloxy)-4-(2-oxoethyl)benzonitrile

Product 1

HCID 569706352-methoxy-4-(2-{4-[2-(3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl)ethyl]piperazin-1-yl}ethyl)benzonitrileYield 63%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a flask containing 3-methyl-6-[2-(piperazin-1-yl)ethyl]-3,4-dihydro-1H-isochromen-1-one hydrochloride (123 mg, 0.40 mmol) was added in 2 mL of EtOH and NaOH (79 μl, 0.40 mmol). The solvent was removed and the free amine redissolved in DCM and filtered directly into a flask containing 2-methoxy-4-(2-oxoethyl)benzonitrile (58 mg, 0.33 mmol). The mixture was allowed to stir for 20 minutes before sodium triacetoxyborohydride (210 mg, 0.99 mmol) was added. The reaction stirred for 1 hour before being quenched with MeOH. The crude reaction was stirred an additional 30 minutes and the excess solvent was removed. The crude material was redissolved in DCM, filtered, concentrated and purified via MPLC [10-50% (10% MeOH in DCM)/DCM)] to afford 90 mg (63% yield) of 2-methoxy-4-(2-{4-[2-(3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl)ethyl]piperazin-1-yl}ethyl)benzonitrile. 1H NMR (500 MHz; DMSO): 7.80 (d, J=8.0 Hz, 1H), 7.58 (d, J=8.0 Hz, 1H), 7.27 (d, J=7.8 Hz, 1H), 7.22 (s, 1H), 7.14 (s, 1H), 6.95 (d, J=7.8 Hz, 1H), 4.65 (m, 1H), 3.88 (bs, 4H), 2.94 (m, 4H), 2.78 (m, 4H), 2.43 (m, 4H), 1.38 (d, J=6.8 Hz, 3H). LC-MS (IE, m/z): 375 [M+1]+. (0.098 μM)

Workup

  1. customThe solvent was removed
  2. dissolutionthe free amine redissolved in DCM
  3. filtrationfiltered directly into a flask
  4. additionwas added
  5. custombefore being quenched with MeOH
  6. customThe crude reaction
  7. stirringwas stirred an additional 30 minutes
  8. customthe excess solvent was removed
  9. dissolutionThe crude material was redissolved in DCM
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified via MPLC [10-50% (10% MeOH in DCM)/DCM)]

Sources & evidence

ORD record
ord-f54f69fe954742aab4b19d813cacc225
Source dataset
uspto-grants-2015_07
Patent number
US09073882B2

Reaction notes

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