1-Methylpiperazine → HCID 178480928, compound

HRID 1947819Notes

Reaction equation

HRID 1947819 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH:13]2[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]2)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2.[CH3:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:13]2[CH2:18][CH2:17][C@H:16]([N:24]3[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]3)[CH2:15][CH2:14]2)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2

Participants

5

Reactant 3

HCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 672561257-amino-2-methyl-4-(4-oxocyclohexyl)-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 178480928HCID 178480928, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 7-amino-2-methyl-4-(4-oxocyclohexyl)-2,3-dihydro-1H-isoindol-1-one (100.0 mg, 0.3871 mmol) in 1,2-dichloroethane (2.0 mL) was charged with 1-methylpiperazine (58.16 mg, 0.5807 mmol) and sodium triacetoxyborohydride (164.1 mg, 0.7743 mmol). The reaction mixture was stirred at rt for 24 hours. The reaction mixture was quenched with NaHCO3 (10 mL) and extracted with EtOAc (20 mL). The organic layer was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield a light yellow oil. The crude material was purified and by silica gel chromatography on the combi-flash Rf system using DCM/7M NH3 in MeOH (100:0→90:10) as eluent to afford the cis isomer (76.5 mg, 58%, first eluting product) and the trans isomer (30.0 mg, 23%, second eluting product). Cis isomer: 1H NMR (CDCl3, 400 MHz): δ=1.42-1.56 (m, 4H), 1.82-1.96 (m, 2H), 2.06 (d, J=11.87 Hz, 2H), 2.27 (br. s., 1H), 2.34 (s, 3H), 2.38-2.78 (m, 9H), 3.14 (s, 3H), 4.31 (s, 2H), 5.08 (s, 2H), 6.58 (d, J=8.34 Hz, 1H), 7.18 (d, J=8.34 Hz, 1H). MS (ES+): m/z 343.25 [MH+]. Trans isomer: 1H NMR (CDCl3, 400 MHz): δ=1.35-1.75 (m, 7H), 1.91 (d, J=12.13 Hz, 2H), 2.03-2.13 (m, 2H), 2.34 (s, 3H), 2.47-2.82 (m, 7H), 3.14 (s, 3H), 4.28 (s, 2H), 5.09 (s, 2H), 6.56 (d, J=8.34 Hz, 1H), 7.09 (d, J=8.34 Hz, 1H). MS (ES+): m/z 343.26 [MH+].

Workup

  1. customThe reaction mixture was quenched with NaHCO3 (10 mL)
  2. extractionextracted with EtOAc (20 mL)
  3. washThe organic layer was washed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto yield a light yellow oil
  8. customThe crude material was purified and by silica gel chromatography on the combi-flash Rf system
  9. customto afford the cis isomer (76.5 mg, 58%, first eluting product)

Sources & evidence

ORD record
ord-8e5c15b023374a12bdce6c4d5c22119d
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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