Carbamate → 5-(Quinolin-5-ylcarbamoyl)-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridine-2-carboxylic acid

HRID 2093055Notes

Reaction equation

Cl.C([O:4][C:5]([C:7]1[S:8][C:9]2[CH2:10][NH:11][CH2:12][CH2:13][C:14]=2[N:15]=1)=[O:6])C.CCN(CC)CC.[C:23](=[O:26])([O-])[NH2:24].[CH:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:30]=[CH:29][N:28]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CO.O>[N:28]1[C:27]2[C:36](=[C:35]([NH:24][C:23]([N:11]3[CH2:12][CH2:13][C:14]4[N:15]=[C:7]([C:5]([OH:4])=[O:6])[S:8][C:9]=4[CH2:10]3)=[O:26])[CH:34]=[CH:33][CH:32]=2)[CH:31]=[CH:30][CH:29]=1

Participants

Conditions

Temperature: 90 °C

Procedure

5-tert-butyl 2-ethyl 6,7-dihydro[1,3]thiazolo[5,4-c]pyridine-2,5(4H)-dicarboxylate obtained in step V of example 1 was deprotected to get the hydrochloride salt of 4,5,6,7-Tetrahydro-thiazolo[5,4-c]pyridine-2-carboxylic acid ethyl ester. To a solution of a HCl salt of 4,5,6,7-Tetrahydro-thiazolo[5,4-c]pyridine-2-carboxylic acid ethyl ester (1.0 eq) in DMF was added Et3N (1.0 eq.) followed by carbamate derivative of Isoquinoline (1.0 eq) obtained in step I above. The reaction mixture was refluxed for 3 h at 90° C. Water was added and the organic layer was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford crude product, which, was hydrolysed by stirring in MeOH: water and K2CO3 (2.0 eq.) for 48 h Reaction mixture was concentrated under reduced pressure and neutralized to pH 7.0 to afford 5-(Quinolin-5-ylcarbamoyl)-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridine-2-carboxylic acid).

Workup

customthe organic layer was separated
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated under reduced pressure
customto afford crude product, which
concentrationwas concentrated under reduced pressure and neutralized to pH 7.0

Sources & evidence

ORD record: ord-03ac15654a1a4d8daa08631d22333b15
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08440830B2

Reaction notes

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