Hexahydro-1,4-diazepine → 7-Cyclopropyl-8-(1,4-diazepan-1-yl)quinoline

HRID 532860Notes

Reaction equation

[NH:1]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.CC([O-])(C)C.[Na+].Br[C:15]1[C:16]([CH:25]2[CH2:27][CH2:26]2)=[CH:17][CH:18]=[C:19]2[C:24]=1[N:23]=[CH:22][CH:21]=[CH:20]2>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:25]1([C:16]2[C:15]([N:1]3[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]3)=[C:24]3[C:19]([CH:20]=[CH:21][CH:22]=[N:23]3)=[CH:18][CH:17]=2)[CH2:27][CH2:26]1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of homopiperazine (0.965 g, 9.6 mmol), NaOt-Bu (0.323 g, 3.4 mmol), (±)-BINAP (0.40 g, 0.64 mmol), and Pd2(dba)3 (0.22 g, 0.24 mmol) in toluene (10 mL) was heated to 110° C. and 8-bromo-7-cyclopropylquinoline (0.60 g, 2.4 mmol) was added. After 2 h, the reaction was cooled to rt, quenched with 50 mL of water, and extracted with EtOAc (2×50 mL). The organic layer was separated, dried over anhydrous Na2SO4, concentrated, and purified by SiO2 chromatography with a gradient elution of 0.25-2.2% NH4OH and 2.5-22% MeOH/CH2Cl2 to yield 7-cyclopropyl-8-(1,4-diazepan-1-yl)quinoline (0.33 g, 51% yield).

Workup

temperaturethe reaction was cooled to rt
customquenched with 50 mL of water
extractionextracted with EtOAc (2×50 mL)
customThe organic layer was separated
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated
custompurified by SiO2 chromatography with a gradient elution of 0.25-2.2% NH4OH and 2.5-22% MeOH/CH2Cl2

Sources & evidence

ORD record: ord-780b7b6cb9a94e4c9e772f20301fa643
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853202B2

Reaction notes

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