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 1776591Notes

Reaction equation

HRID 1776591 reaction equation
[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]

Participants

6

Reactant 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

Product 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-oxideYield 39.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-bc5750da63054e2f980bd5e8ae26fe54
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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