Sodium hydride → 1-(8-Bromo-quinolin-2-yl)-6,7-dihydro-1H-5,8-dioxa-1,3-diaza-cyclopenta[b]naphthalene

HRID 1745912Notes

Reaction equation

[NH:1]1[C:5]2=[CH:6][C:7]3[O:8][CH2:9][CH2:10][O:11][C:12]=3[CH:13]=[C:4]2[N:3]=[CH:2]1.[H-].[Na+].[Br:16][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[C:26]=1[N:25]=[C:24](Cl)[CH:23]=[CH:22]2>CN1CCCC1=O>[Br:16][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[C:26]=1[N:25]=[C:24]([N:1]1[C:5]3=[CH:6][C:7]4[O:8][CH2:9][CH2:10][O:11][C:12]=4[CH:13]=[C:4]3[N:3]=[CH:2]1)[CH:23]=[CH:22]2

Participants

Conditions

Temperature: 65 °C

Procedure

6,7-Dihydro-1H-5,8-dioxa-1,3-diaza-cyclopenta[b]naphthalene 81B (600 mg, 3,4 mMol) was dissolved in 15 mL of 1-methyl-2-pyrrolidinone under an atmosphere of dry N2. To this solution was added 60% sodium hydride in oil (136 mg, 3.40 mMol) and the reaction mixture was stirred for 15 minutes. 8-Bromo-2-chloro-quinoline 81A (750 mg, 3.10 mMol) was then added to the reaction mixture which was subsequently heated to 65° C. and reacted at this temperature overnight. The reaction mixture was then cooled to ambient temperature, partitioned between DCM and saturated aqueous NaHCO3, washed again with saturated aqueous NaHCO3, dried over Na2SO4, filtered and concentrated under vacuum to give 1.60 g of an orange solid. The solid was chromatographed on flash silica gel eluting with a gradient from DCM to MeOH/DCM (0.5/99.5) to give 700 mg of the title compound 81C as a light yellow solid.

Workup

customreacted at this temperature overnight
temperatureThe reaction mixture was then cooled to ambient temperature
custompartitioned between DCM and saturated aqueous NaHCO3
washwashed again with saturated aqueous NaHCO3
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-84975314456948d1ab3ec1a0f26d990f
Source dataset: uspto-grants-2006_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07019147B1

Reaction notes

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