Cesium carbonate → 17-[2-(2-Isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.0*4,6*]octadec-7-ene-4-carboxylic acid ethyl ester

HRID 2242459Notes

Reaction equation

HRID 2242459 reaction equation
[CH:1]([NH:4][C:5]1[S:6][CH:7]=[C:8]([C:10]2[CH:19]=[C:18]([OH:20])[C:17]3[C:12](=[CH:13][C:14]([O:21][CH3:22])=[CH:15][CH:16]=3)[N:11]=2)[N:9]=1)([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:29]([O:31][C:32]([C:34]12[CH2:51][CH:50]1[CH:49]=[CH:48][CH2:47][CH2:46][CH2:45][CH2:44][N:43]([CH3:52])[C:42](=[O:53])[CH:41]1[CH:37]([CH2:38][CH:39](OS(C3C=CC(Br)=CC=3)(=O)=O)[CH2:40]1)[C:36](=[O:65])[NH:35]2)=[O:33])[CH3:30]>CN1C(=O)CCC1.C(Cl)(Cl)Cl>[CH2:29]([O:31][C:32]([C:34]12[CH2:51][CH:50]1[CH:49]=[CH:48][CH2:47][CH2:46][CH2:45][CH2:44][N:43]([CH3:52])[C:42](=[O:53])[CH:41]1[CH:37]([CH2:38][CH:39]([O:20][C:18]3[C:17]4[C:12](=[CH:13][C:14]([O:21][CH3:22])=[CH:15][CH:16]=4)[N:11]=[C:10]([C:8]4[N:9]=[C:5]([NH:4][CH:1]([CH3:3])[CH3:2])[S:6][CH:7]=4)[CH:19]=3)[CH2:40]1)[C:36](=[O:65])[NH:35]2)=[O:33])[CH3:30]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 72530353HCID 72530353, compoundHCID 178487686HCID 178487686, compound

Product 1

HCID 7276956117-[2-(2-Isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.0*4,6*]octadec-7-ene-4-carboxylic acid ethyl esterYield 13%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
60 °C

Procedure

2-(Isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-ol (220 mg, 0.7 mmol) (prepared as described in WO 00/59929) was dissolved in 7 ml of NMP (N-methyl pyrrolidinone), one spoon of Cs2CO3 was added, stirred at 60° C. for 1.5 h. Then compound 108 (150 mg, 0.24 mmol) was added. The reaction mixture was stirred at 80° C. overnight. Was diluted with chloroform and washed with sodium bicarbonate, brine. Water phases were back-extracted with chloroform. The combined organic layers were dried over sodium sulphate and evaporated. The crude product was purified by preparative HPLC (Gilson) (MeOH—H2O, 65%) to give 21 mg of product (yield 13%) as well as 12 mg of isomer.

Workup

  1. stirringThe reaction mixture was stirred at 80° C. overnight
  2. washwashed with sodium bicarbonate, brine
  3. extractionWater phases were back-extracted with chloroform
  4. dry with materialThe combined organic layers were dried over sodium sulphate
  5. customevaporated
  6. customThe crude product was purified by preparative HPLC (Gilson) (MeOH—H2O, 65%)

Sources & evidence

ORD record
ord-b42b5ccd85414d52a3deff8f21ab4a1f
Source dataset
uspto-grants-2010_03
Patent number
US07671032B2

Reaction notes

Loading…