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

HRID 518268ノート

反応式

HRID 518268 の反応式
[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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-2ce101c1f38a43e89645673bdb3830e6
出典データセット
uspto-grants-2015_08
特許番号
US09115141B2

反応ノート

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