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Water → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-methoxy-3-(N-(2-morpholinoethyl)methylsulfonamido)phenoxy)carbonyloxy)-ethyl)pyridine 1-oxide

HRID 1776591
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HRID 1776591 반응식
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:39])[CH:5]=[C:6]([Cl:38])[C:7]=1[CH2:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:32])[F:31])=[C:25]([O:33][CH2:34][CH:35]2[CH2:37][CH2:36]2)[CH:24]=1)[O:10][C:11]([O:13]C1C=CC([N+]([O-])=O)=CC=1)=[O:12].O[C:41]1[CH:42]=[CH:43][C:44]([O:60][CH3:61])=[C:45]([N:47]([CH2:52][CH2:53][N:54]2[CH2:59][CH2:58][O:57][CH2:56][CH2:55]2)[S:48]([CH3:51])(=[O:50])=[O:49])[CH:46]=1.O>CN(C1C=CN=CC=1)C.CN(C=O)C>[Cl:38][C:6]1[CH:5]=[N+:4]([O-:39])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:32])[F:31])=[C:25]([O:33][CH2:34][CH:35]2[CH2:36][CH2:37]2)[CH:24]=1)[O:10][C:11]([O:13][C:41]1[CH:42]=[CH:43][C:44]([O:60][CH3:61])=[C:45]([N:47]([CH2:52][CH2:53][N:54]2[CH2:55][CH2:56][O:57][CH2:58][CH2:59]2)[S:48]([CH3:51])(=[O:50])=[O:49])[CH:46]=1)=[O:12]
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참가 물질

6

반응물 3

HCID 962WaterHCID 86679418(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)-carbonyloxy)ethyl)pyridine 1-oxideHCID 86679542N-(5-hydroxy-2-methoxyphenyl)-N-(2-morpholinoethyl)methanesulfonamide

생성물 1

HCID 71543109(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-methoxy-3-(N-(2-morpholinoethyl)methylsulfonamido)phenoxy)carbonyloxy)-ethyl)pyridine 1-oxide
수율 39.2%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

To a solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)carbonyloxy)ethyl)pyridine I-oxide (prepared in an analogous manner to that described in Scheme 3, Step 1) (0.250 g, 0.427 mmol) and DMAP (0.052 g, 0.427 mmol) in dry DMF (5 ml), N-(5-hydroxy-2-methoxyphenyl)-N-(2-morpholinoethyl)methanesulfonamide (0.180 g, 0.545 mmol) was added, and the resulting mixture was stirred at RT for 7 hours. The reaction mixture was treated with water and extracted with DCM (3×). The combined organic layers were washed with brine and dried over Na2SO4; the solvent was removed under vacuum and the crude was purified by flash chromatography on silica gel column (DCM:acetone=6:4) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-methoxy-3-(N-(2-morpholinoethyl)methylsulfonamido)phenoxy)carbonyloxy)-ethyl)pyridine 1-oxide (0.130 g, 0.167 mmol, 39.2% yield, LC-MS purity (BPI): 100%, MS/ESI+ 776.34 [MH]+, [δD]−27.42, c=0.542, DCM).

후처리

  1. additionwas added
  2. extractionextracted with DCM (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent was removed under vacuum
  6. customthe crude was purified by flash chromatography on silica gel column (DCM:acetone=6:4)

출처 및 근거

ORD 기록
ord-bc5750da63054e2f980bd5e8ae26fe54
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09265768B2

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