Hydrochloric Acid → (S)-(9H-fluoren-9-yl)methyl 1-(8-chloro-1-(tetrahydro-2H-pyran-4-ylcarbamoyl)isoquinolin-3-yl)ethylcarbamate

HRID 1626937노트

반응식

HRID 1626937 반응식
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:21]3[N:22]=[C:23]([C:32]([OH:34])=O)[C:24]4[C:29]([CH:30]=3)=[CH:28][CH:27]=[CH:26][C:25]=4[Cl:31])[CH3:20])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[O:46]1[CH2:51][CH2:50][CH:49]([NH2:52])[CH2:48][CH2:47]1.CCN(CC)CC.Cl>C(Cl)Cl.O>[Cl:31][C:25]1[CH:26]=[CH:27][CH:28]=[C:29]2[C:24]=1[C:23]([C:32](=[O:34])[NH:52][CH:49]1[CH2:50][CH2:51][O:46][CH2:47][CH2:48]1)=[N:22][C:21]([C@@H:19]([NH:18][C:16](=[O:17])[O:15][CH2:14][CH:12]1[C:11]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[C:5]3[C:13]1=[CH:1][CH:2]=[CH:3][CH:4]=3)[CH3:20])=[CH:30]2

참가 물질

9

반응물 6

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 4192234-AminotetrahydropyranHCID 71232891(S)-3-(1-(((9H-fluoren-9-yl)methoxy)carbonylamino)ethyl)-8-chloroisoquinoline-1-carboxylic acid

생성물 1

HCID 69097730(S)-(9H-fluoren-9-yl)methyl 1-(8-chloro-1-(tetrahydro-2H-pyran-4-ylcarbamoyl)isoquinolin-3-yl)ethylcarbamate

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (S)-3-(1-(((9H-fluoren-9-yl)methoxy)carbonylamino)ethyl)-8-chloroisoquinoline-1-carboxylic acid (349) (25.5 g, 54.0 mmol, 1.0 eq) and DMF (1.5 mL, 19.3 mmol, 0.35 eq) in CH2Cl2 (200 mL), oxalyl chloride (30 mL, 177.7 mmol, 3.29 eq) was added dropwise slowly. The resulting mixture was stirred at RT for 1 h. The reaction mixture was concentrated in vacuo and the residue was dissolved in CH2Cl2 (100 mL). This solution was added dropwise to a solution of tetrahydro-2H-pyran-4-amine (15 mL, 133 mmol, 2.46 eq) and Et3N (30 mL, 210.9 mmol, 3.90 eq) in CH2Cl2 (200 mL) at 0° C. The mixture was warmed to RT and stirred for 30 min. 5% Hydrochloric acid aqueous solution was added to the reaction mixture until the pH=1˜2. The mixture was poured into water (400 mL), extracted with CH2Cl2 (150 mL×2). The organic layer was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (5-10% MeOH-DCM) to afford (S)-(9H-fluoren-9-yl)methyl 1-(8-chloro-1-(tetrahydro-2H-pyran-4-ylcarbamoyl)isoquinolin-3-yl)ethylcarbamate (351).

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in CH2Cl2 (100 mL)
  3. temperatureThe mixture was warmed to RT
  4. stirringstirred for 30 min
  5. extractionextracted with CH2Cl2 (150 mL×2)
  6. dry with materialThe organic layer was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customThe residue was purified by flash column chromatography on silica gel (5-10% MeOH-DCM)

출처 및 근거

ORD 기록
ord-0b9d6e883e0345e29423969854404fa9
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785470B2

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