Diisopropylethylamine → 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)-1H-[1,3]oxazino[5,4-c]quinoline-2,4-dione

HRID 336883Notes

Reaction equation

HRID 336883 reaction equation
[C:1]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([C:28]5[CH:29]=[N:30][C:31]6[C:36]([CH:37]=5)=[CH:35][CH:34]=[CH:33][CH:32]=6)[CH:26]=4)[N:21]=[CH:20][C:19]=3[C:38]([OH:40])=[O:39])=[CH:13][C:12]=2[C:41]([F:44])([F:43])[F:42])[CH2:7][CH2:6]1)(=[O:4])[CH2:2][CH3:3].Cl[C:46](Cl)([O:48]C(=O)OC(Cl)(Cl)Cl)Cl.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([N:5]1[CH2:6][CH2:7][N:8]([C:11]2[CH:16]=[CH:15][C:14]([N:17]3[C:18]4[C:27]5[CH:26]=[C:25]([C:28]6[CH:29]=[N:30][C:31]7[C:36]([CH:37]=6)=[CH:35][CH:34]=[CH:33][CH:32]=7)[CH:24]=[CH:23][C:22]=5[N:21]=[CH:20][C:19]=4[C:38](=[O:40])[O:39][C:46]3=[O:48])=[CH:13][C:12]=2[C:41]([F:42])([F:43])[F:44])[CH2:9][CH2:10]1)(=[O:4])[CH2:2][CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 497830314'-(4-(4-Propionylpiperazin-1-yl)-3(trifluoromethyl)phenylamino)-3,6'-biquinoline-3'-carboxylic acid

Product 1

HCID 461915741-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)-1H-[1,3]oxazino[5,4-c]quinoline-2,4-dioneYield 6.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The crude compound 5.5 4′-(4-(4-propionylpiperazin-1-yl)-3(trifluoromethyl)phenylamino)-3,6′-biquinoline-3′-carboxylic acid (20 mg, 0.033 mmol, 1 equiv.) in CH2Cl2 (3 mL) at 0° C. was added triphosgene (10 mg, 0.033 mmol, 1 equiv.) and DIEA (17 μL, 0.1 mmol, 3 equiv.). The resulting solution was warmed to room temperature in 3 hours and further stirred for 1 hour before being quenched with NaHCO3 (sat. 1 mL) and extracted with CH2Cl2 (5 mL×2). The organic phase was dried over Na2SO4 and the residue was purified via preparative LC-MS (CH3CN:H2O) to afford the desired product 5.6 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)-1H-[1,3]oxazino[5,4-c]quinoline-2,4-dione (1.3 mg). LC-MS(M+H): 626.20

Workup

  1. custombefore being quenched with NaHCO3 (sat. 1 mL)
  2. extractionextracted with CH2Cl2 (5 mL×2)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. customthe residue was purified via preparative LC-MS (CH3CN:H2O)

Sources & evidence

ORD record
ord-96253b90d425489ea469a4872822f063
Source dataset
uspto-grants-2014_11
Patent number
US08889706B2

Reaction notes

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