Acetic Acid → 1-Methyl-3-[({[3-(4-methylpiperazin-1-yl)-2,3,4,5-tetrahydrooxepin-3-yl]methyl}amino)methyl]quinolin-2(1H)-one

HRID 1943014Notes

Reaction equation

HRID 1943014 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2([CH2:15][NH2:16])[CH2:14][CH2:13][CH:12]=[CH:11][O:10][CH2:9]2)[CH2:4][CH2:3]1.CC(O)=O.[CH3:21][N:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[C:24]([CH:32]=O)[C:23]1=[O:34].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.[OH-].[Na+]>[CH3:21][N:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[C:24]([CH2:32][NH:16][CH2:15][C:8]2([N:5]3[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]3)[CH2:14][CH2:13][CH:12]=[CH:11][O:10][CH2:9]2)[C:23]1=[O:34]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 49146281-Methyl-2-oxo-1,2-dihydroquinoline-3-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 584159261-[3-(4-Methylpiperazin-1-yl)-2,3,4,5-tetrahydrooxepin-3-yl]methanamine

Product 1

HCID 584159511-Methyl-3-[({[3-(4-methylpiperazin-1-yl)-2,3,4,5-tetrahydrooxepin-3-yl]methyl}amino)methyl]quinolin-2(1H)-oneYield 69.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 1-[3-(4-methylpiperazin-1-yl)-2,3,4,5-tetrahydrooxepin-3-yl]methanamine (250 mg, 1.109 mmole) in 1,2-dichloroethane (4 ml) was added AcOH (290 μL, 5.07 mmole) then 1-methyl-2-oxo-1,2-dihydroquinoline-3-carbaldehyde (190 mg, 1.015 mmole). After 20 min sodium triacetoxyborohydride (323 mg, 1.522 mmole) was added. After 16 hr the mixture was diluted with 1M aqueous NaOH and extracted with CH2Cl2 (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash column chromatography (gradient, 0-10% MeOH/CH2Cl2) gave the title compound as a pale yellow oil (279 mg, 69%). 1H-NMR (CDCl3, 500 MHz) d 7.70 (s, 1 H), 7.56 (m, 2 H), 7.35 (d, J=8.30 Hz, 1 H), 7.25 (m, 1 H), 6.24 (d, J=6.6 Hz, 1 H), 4.59 (m, 1 H), 4.25 (dd AB, J=12.94 and 44.19 Hz, 2 H), 3.80 (m, 2 H), 3.74 (s, 3 H), 2.71-2.61 (m, 6 H), 2.44 (m, 4 H), 2.28 (s, 3 H), 2.21-2.06 (m, 4 H), 1.51 (m, 1 H).

Workup

  1. extractionextracted with CH2Cl2 (3×)
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-8c4aa99377714e65b48cde9d5bf50d7a
Source dataset
uspto-grants-2013_03
Patent number
US08389720B2

Reaction notes

Loading…