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Dichloromethane → Ethyl 3-(5-amino-2-(4-(2-(3-(diethoxyphosphoryl)-3,3-difluoropropoxy)ethoxy)-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)propanoate

HRID 2167669
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HRID 2167669 반응식
[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][C:15]=3[CH3:21])=[CH:7][C:6]=2[C:5]2[CH:22]=[CH:23][C:24]([CH2:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:25][C:4]=2[N:3]=1.Br[CH2:34][CH2:35][O:36][CH2:37][CH2:38][C:39]([P:42](=[O:49])([O:46][CH2:47][CH3:48])[O:43][CH2:44][CH3:45])([F:41])[F:40].C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>CN(C=O)C>[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:34][CH2:35][O:36][CH2:37][CH2:38][C:39]([P:42]([O:43][CH2:44][CH3:45])([O:46][CH2:47][CH3:48])=[O:49])([F:40])[F:41])=[CH:16][C:15]=3[CH3:21])=[CH:7][C:6]=2[C:5]2[CH:22]=[CH:23][C:24]([CH2:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:25][C:4]=2[N:3]=1
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참가 물질

6

반응물 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 58166526Diethyl 3-(2-bromoethoxy)-1,1-difluoropropylphosphonateHCID 67065545Ethyl 3-(5-amino-2-(4-hydroxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)propanoate

생성물 1

HCID 86651456Ethyl 3-(5-amino-2-(4-(2-(3-(diethoxyphosphoryl)-3,3-difluoropropoxy)ethoxy)-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)propanoate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
60 °C

실험 절차

To a solution of ethyl 3-(5-amino-2-(4-hydroxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)propanoate (6-13) (1.0 equiv.) dissolved in DMF (0.14 M) was added a solution of diethyl 3-(2-bromoethoxy)-1,1-difluoropropylphosphonate (6-14: described in Example 7—Step 1) (1.3 equiv.) in DMF (0.7 M) and cesium carbonate (4 equiv.). The reaction was stirred at 60° C. After 1.5 hours (or until reaction is complete by LCMS), DCM (2 volume equivalent) was added to the reaction. The solids (inorganic) were filtered, and the filtrate was concentration. The crude product was purified by Combiflash using 0-5% MeOH in DCM to give ethyl 3-(5-amino-2-(4-(2-(3-(diethoxyphosphoryl)-3,3-difluoropropoxy)ethoxy)-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)propanoate (6-15) as an oil which upon standing became a white solid.

후처리

  1. additionwas added to the reaction
  2. filtrationThe solids (inorganic) were filtered
  3. concentrationconcentration
  4. customThe crude product was purified by Combiflash

출처 및 근거

ORD 기록
ord-24518c82082048808461a954206e098b
출처 데이터셋
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09045470B2

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