Hydrochloric Acid → 17-[2-(4-Isopropyl-thiazol-2-yl)-7-methoxy-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid

HRID 1516669Notes

Reaction equation

HRID 1516669 reaction equation
C([O:3][C:4]([C:6]12[CH2:23][CH:22]1[CH:21]=[CH:20][CH2:19][CH2:18][CH2:17][CH2:16][N:15]([CH3:24])[C:14](=[O:25])[CH:13]1[CH:9]([CH2:10][CH:11]([O:26][C:27]3[C:36]4[C:31](=[CH:32][C:33]([O:37][CH3:38])=[CH:34][CH:35]=4)[N:30]=[C:29]([C:39]4[S:40][CH:41]=[C:42]([CH:44]([CH3:46])[CH3:45])[N:43]=4)[CH:28]=3)[CH2:12]1)[C:8](=[O:47])[NH:7]2)=[O:5])C.[Li+].[OH-].Cl>O1CCOCC1.CO>[CH:44]([C:42]1[N:43]=[C:39]([C:29]2[CH:28]=[C:27]([O:26][CH:11]3[CH2:10][CH:9]4[CH:13]([C:14](=[O:25])[N:15]([CH3:24])[CH2:16][CH2:17][CH2:18][CH2:19][CH:20]=[CH:21][CH:22]5[C:6]([C:4]([OH:5])=[O:3])([NH:7][C:8]4=[O:47])[CH2:23]5)[CH2:12]3)[C:36]3[C:31](=[CH:32][C:33]([O:37][CH3:38])=[CH:34][CH:35]=3)[N:30]=2)[S:40][CH:41]=1)([CH3:46])[CH3:45]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 6741035617-[2-(4-Isopropyl-thiazol-2-yl)-7-methoxy-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid ethyl ester

Product 1

HCID 6741069117-[2-(4-Isopropyl-thiazol-2-yl)-7-methoxy-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acidYield 94.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 17-[2-(4-isopropyl-thiazol-2-yl)-7-methoxy-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid ethyl ester (34, 182 mg, 0.275 mmol) in dioxane (3 mL) and MeOH (1.5 mL) was added a 1 M aqueous solution of LiOH (3 mL). After 72 h, the reaction mixture was successively acidified to pH 2 with 1.7 M HCl and evaporated under vacuum. Then, 1 g of silica was added towards the end to adsorb the crude product. Purification by flash column chromatography (15 g YMC silica; gradient MeOH/CH2Cl2: 200 mL each 2%, 4%, 6%, 100 mL each 8%, 10%; forefraction 100 mL followed by 15-mL fractions, desired product fractions 33-42) gave 164 mg (94%) of the title product 35 as a yellow solid: Rf (10% MeOH—CH2Cl2)=0.38.

Workup

  1. customevaporated under vacuum
  2. additionThen, 1 g of silica was added towards the end
  3. customPurification by flash column chromatography (15 g YMC silica; gradient MeOH/CH2Cl2: 200 mL each 2%, 4%, 6%, 100 mL each 8%, 10%; forefraction 100 mL followed by 15-mL fractions, desired product fractions 33-42)

Sources & evidence

ORD record
ord-ecb5ed29790a46d49009775b81689639
Source dataset
uspto-grants-2012_07
Patent number
US08227407B2

Reaction notes

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