1,3-Dihydro-1,3-dioxo-2H-isoindole-2-butanal → 2-[4-(5,6,7,8-Tetrahydroquinolin-8-ylamino)-butyl]-isoindole-1,3-dione

HRID 899741Notes

Reaction equation

HRID 899741 reaction equation
[N:1]1[C:10]2[CH:9]([NH2:11])[CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[O:12]=[C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](=[O:22])[N:14]1[CH2:23][CH2:24][CH2:25][CH:26]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[N:1]1[C:10]2[CH:9]([NH:11][CH2:26][CH2:25][CH2:24][CH2:23][N:14]3[C:15](=[O:22])[C:16]4[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=4)[C:13]3=[O:12])[CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 771501,3-Dihydro-1,3-dioxo-2H-isoindole-2-butanalHCID 5049666Sodium triacetoxyborohydrideHCID 113555648-Amino-5,6,7,8-tetrahydroquinoline

Product 1

HCID 589971372-[4-(5,6,7,8-Tetrahydroquinolin-8-ylamino)-butyl]-isoindole-1,3-dioneYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-[4-(5,6,7,8-Tetrahydro-quinolin-8-ylamino)-butyl]-isoindole-1,3-dione was prepared following the general procedure B for reductive amination. To a solution of 5,6,7,8-Tetrahydro-quinolin-8-ylamine (1.0609 g, 7.1 mmol) and 4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-butyraldehyde (1.4079 g, 6.8 mmol) (prepared according to the procedure for COMPOUND 18) in methylene chloride (64 mL) was added NaBH(OAc)3 (4.07 g, 19.2 mmol) and the reaction stirred at room temperature for two hours. The reaction was quenched with 1N NaOH (45 mL), extracted with methylene chloride (2×55 mL), dried (Na2SO4), filtered, and concentrated. Purification of the crude material by column chromatography on silica gel (40:1:1 CH2Cl2—MeOH—NH4OH) provided 1.16 g (52%) of 2-[4-(5,6,7,8-Tetrahydro-quinolin-8-ylamino)-butyl]-isoindole-1,3-dione. 1H NMR (CDCl3) δ 1.57-1.66 (m, 3H), 1.69-1.84 (m, 4H). 1.93-2.03 (m, 1H), 2.07-2.13 (m, 1H), 2.69-2.86 (m, 4H), 3.70-3.77 (m, 3H), 7.03-7.07 (m, 1H), 7.35 (d, 1H, J=7.2 Hz), 7.67-7.73 (m, 2H), 7.80-7.85 (m, 2H), 8.37 (d, 1H, J=3 Hz).

Workup

  1. custom2-[4-(5,6,7,8-Tetrahydro-quinolin-8-ylamino)-butyl]-isoindole-1,3-dione was prepared
  2. customThe reaction was quenched with 1N NaOH (45 mL)
  3. extractionextracted with methylene chloride (2×55 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography on silica gel (40:1:1 CH2Cl2—MeOH—NH4OH)

Sources & evidence

ORD record
ord-7e2c6680655648c8a3777ddee2e09092
Source dataset
uspto-grants-2008_04
Patent number
US07354934B2

Reaction notes

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