Dimethylamine → 7-amino-4-[4-(dimethylamino)cyclohexyl]-2-methyl-2,3-dihydro-1H-isoindol-1-one

HRID 511483노트

반응식

HRID 511483 반응식
[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][NH:21][CH3:22].C1COCC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH:13]2[CH2:18][CH2:17][CH:16]([N:21]([CH3:22])[CH3:20])[CH2:15][CH2:14]2)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2

참가 물질

6

반응물 4

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 5049666Sodium triacetoxyborohydrideHCID 672561257-amino-2-methyl-4-(4-oxocyclohexyl)-2,3-dihydro-1H-isoindol-1-one

생성물 1

HCID 672542857-amino-4-[4-(dimethylamino)cyclohexyl]-2-methyl-2,3-dihydro-1H-isoindol-1-one수율 58%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

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 2.0 M of dimethylamine in THF (0.2903 mL, 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 by silica gel chromatography on the combi-flash Rf system using DCM/7M NH3 in MeOH (100:0→90:10) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield a light yellow solid, 64.7 mg (58% yield). 1H NMR (CDCl3, 400 MHz): δ=1.53 (d, J=11.12 Hz, 4 H), 1.91 (d, J=11.12 Hz, 2 H), 2.08 (d, J=14.65 Hz, 2 H), 2.31 (br. s., 6 H), 2.45 (br. s., 1 H), 2.48-2.58 (m, 1 H), 3.14 (s, 3 H), 4.30 (s, 2 H), 5.07 (br. s., 2 H), 6.57 (d, J=8.34 Hz, 1 H), 7.26 (br. s., 1 H). MS (ES+): m/z 288.21 [MH+] (TOF, polar).

후처리

  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 by silica gel chromatography on the combi-flash Rf system
  9. additionThe fractions containing product
  10. concentrationconcentrated under reduced pressure
  11. customto yield a light yellow solid, 64.7 mg (58% yield)

출처 및 근거

ORD 기록
ord-65a8dcad25fe475b83ad5e87b5752de4
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096624B2

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