Sodium hydride → HCID 21101941, compound

HRID 1353357Notes

Reaction equation

[H-].[Na+].[Cl:3][C:4]1[CH:13]=[C:12]2[C:7]([C:8](=O)[CH2:9][CH:10]=[N:11]2)=[CH:6][CH:5]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH:26]([CH3:28])[NH:25][CH2:24][CH:23]1[CH3:29])=[O:21])([CH3:18])([CH3:17])[CH3:16]>CN(C=O)C>[C:15]([O:19][C:20]([N:22]1[CH:23]([CH3:29])[CH2:24][N:25]([C:8]2[C:7]3[C:12](=[CH:13][C:4]([Cl:3])=[CH:5][CH:6]=3)[N:11]=[CH:10][CH:9]=2)[CH:26]([CH3:28])[CH2:27]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

Conditions

Temperature: 80 °C

Procedure

Sodium hydride (72 mg, 3 mmol) is added to a solution of 7-chloro-4-quinolone (359 mg, 2 mmol) in DMF. After 1 h at 40° C. N-phenyl(trifluoromethylsulfon)imide (1.0 g, 2.8 mmol) and, 1 h later, 1-tert-butoxycarbonyl-2,5-dimethylpiperazine (1.8 g, 8 mmol) is added. The reaction mixture is stirred at 80° C. for 2 days, concentrated, diluted with EtOAc, washed with water and brine, dried (Na2SO4), and concentrated. The residue is purified by reversed phase HPLC with water-MeCN-TFA to give 4-[4-(tert-butoxycarbonyl)-2,5-dimethylpiperazin-1-yl]-7-chloroquinoline (188 mg, 0.5 mmol) which is deprotected with TFA in CH2Cl2 and transformed after being washed with base into the product with 4-fluorophenyl isocyanate (31 μL, 0.27 mmol) according to method C giving the title product as a colorless solid.

Workup

concentrationconcentrated
additiondiluted with EtOAc
washwashed with water and brine
dry with materialdried (Na2SO4)
concentrationconcentrated
customThe residue is purified by reversed phase HPLC with water-MeCN-TFA

Sources & evidence

ORD record: ord-79e5523f9ec94601abf16d5f4ceb4712
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07220856B2

Reaction notes

Loading…