Citric Acid → Cyclopropanesulfonic acid {17-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methyl-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo-[13.3.0.04,6]octadec-7-ene-4-carbonyl}-amide

HRID 1803694Notes

Reaction equation

HRID 1803694 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[CH:17]=[C:16]([O:18][CH:19]3[CH2:36][CH:35]4[CH:21]([C:22](=[O:42])[N:23]([CH3:41])[CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH:29][CH:30]5[C:32]([C:38]([OH:40])=O)([NH:33][C:34]4=[O:37])[CH2:31]5)[CH2:20]3)[C:15]3[C:10](=[C:11]([CH3:45])[C:12]([O:43][CH3:44])=[CH:13][CH:14]=3)[N:9]=2)[CH:5]=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:58]1([S:61]([NH2:64])(=[O:63])=[O:62])[CH2:60][CH2:59]1.C1CCN2C(=NCCC2)CC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[CH:17]=[C:16]([O:18][CH:19]3[CH2:36][CH:35]4[CH:21]([C:22](=[O:42])[N:23]([CH3:41])[CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH:29][CH:30]5[C:32]([C:38]([NH:64][S:61]([CH:58]6[CH2:60][CH2:59]6)(=[O:63])=[O:62])=[O:40])([NH:33][C:34]4=[O:37])[CH2:31]5)[CH2:20]3)[C:15]3[C:10](=[C:11]([CH3:45])[C:12]([O:43][CH3:44])=[CH:13][CH:14]=3)[N:9]=2)[CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 311Citric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 7667481117-[2-(6-Methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yl-oxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid

Product 1

HCID 76674791Cyclopropanesulfonic acid {17-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methyl-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo-[13.3.0.04,6]octadec-7-ene-4-carbonyl}-amideYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of the acid 17-[2-(6-methyl-2-pyridyl)-7-methoxy-8-methylquinolin-4-yl-oxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid (102, 28 mg, 0.046 mmol) and CDI (15 mg, 0.092 mmol) in dry THF (3 mL) was heated at reflux for 2 h under nitrogen. The activation was monitored by LC-MS. The reaction mixture was cooled at room temperature and cyclopropylsulfonamide (17 mg, 0.137 mmol) was added. Then, DBU (16 μL, 0.105 mmol) was added and the reaction was heated at 55° C. After 24 h, the pH of the reaction mixture was adjusted to 3 with citric acid (5%). Then, the solvent was evaporated, and the residue partitioned between AcOEt and water. The crude material was purified by preparative HPLC to give 17 mg (52%) of the target compound 103: m/z=716 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h under nitrogen
  3. temperaturethe reaction was heated at 55° C
  4. customThen, the solvent was evaporated
  5. customthe residue partitioned between AcOEt and water
  6. customThe crude material was purified by preparative HPLC

Sources & evidence

ORD record
ord-8c2e100c9806427daac466c988e4f606
Source dataset
uspto-grants-2013_01
Patent number
US08349869B2

Reaction notes

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