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

HRID 2093055노트

반응식

HRID 2093055 반응식
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

참가 물질

10

반응물 6

HCID 276CarbamateHCID 313Hydrochloric AcidHCID 8405IsoquinolineHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 53393419Ethyl 4,5,6,7-tetrahydrothiazolo[5,4-C]pyridine-2-carboxylate

생성물 1

HCID 668650425-(Quinolin-5-ylcarbamoyl)-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridine-2-carboxylic acid

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매2회HCID 6228Dimethylformamide용매

반응 조건

온도
90 °C

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-03ac15654a1a4d8daa08631d22333b15
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08440830B2

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