1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (8S,11R,15R)-11-(((9H-fluoren-9-yl)methoxy)carbonylamino)-8-ethyl-2,2-dimethyl-4,10-dioxo-3,6-dioxa-13-thia-9-azahexadecane-15,16-diyl didodecanoate

HRID 2204988ノート

反応式

HRID 2204988 の反応式
[C:1]([O:14][C@H:15]([CH2:41][O:42][C:43](=[O:55])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[CH2:16][S:17][CH2:18][C@@H:19]([C:38](O)=[O:39])[NH:20][C:21](=[O:37])[O:22][CH2:23][CH:24]1[C:36]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:30]2[C:25]1=[CH:26][CH:27]=[CH:28][CH:29]=2)(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[NH2:56][C@@H:57]([CH2:68][CH3:69])[CH2:58][O:59][CH2:60][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(OCC)(=O)C.C1COCC1.CN(C=O)C>[C:1]([O:14][C@H:15]([CH2:41][O:42][C:43](=[O:55])[CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[CH2:16][S:17][CH2:18][C@H:19]([NH:20][C:21]([O:22][CH2:23][CH:24]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:30]=2[C:31]2[C:36]1=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:37])[C:38](=[O:39])[NH:56][C@@H:57]([CH2:68][CH3:69])[CH2:58][O:59][CH2:60][C:61](=[O:62])[O:63][C:64]([CH3:65])([CH3:67])[CH3:66])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]

参加物

8

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67414703(5R,9R)-9-(dodecanoyloxy)-1-(9H-fluoren-9-yl)-3,12-dioxo-2,11-dioxa-7-thia-4-azatricosane-5-carboxylic acidHCID 87385354(S)-tert-butyl 2-(2-aminobutoxy)acetate

生成物 1

HCID 86678282(8S,11R,15R)-11-(((9H-fluoren-9-yl)methoxy)carbonylamino)-8-ethyl-2,2-dimethyl-4,10-dioxo-3,6-dioxa-13-thia-9-azahexadecane-15,16-diyl didodecanoate

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 21974620tetrahydrofuran N,N-dimethylformamide溶媒

実験手順

To a solution of (5R,9R)-9-(dodecanoyloxy)-1-(9H-fluoren-9-yl)-3,12-dioxo-2,11-dioxa-7-thia-4-azatricosane-5-carboxylic acid (6, 1 eq) and (S)-tert-butyl 2-(2-aminobutoxy)acetate (1.5 eq, from the previous step) in 2:1 THF/DMF (0.13 M) was added EDCI (1.3 eq), HOBT (1.3 eq), and DIEA (5 eq). The reaction was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with 2:1 saturated aqueous NaHCO3/water, brine, dried over anhydrous Na2SO4, and concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using a gradient of 0-40% ethyl acetate in hexanes to give the product.

後処理

  1. washThe organic layer was washed with 2:1 saturated aqueous NaHCO3/water, brine
  2. dry with materialdried over anhydrous Na2SO4
  3. concentrationconcentrated en vaccuo
  4. customThe crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  5. customto give the product

出典と根拠

ORDレコード
ord-00381a7d7c264e32963e2e1824d16d30
出典データセット
uspto-grants-2016_06
特許番号
US09365506B2

反応ノート

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