Dimethylformamide → N-(1-{4'-[3-Methyl-4-(5-(3-methyl-phenyl)-pyridin-3-ylamino)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarbonyl)-methanesulfonamide

HRID 45605Notes

Reaction equation

HRID 45605 reaction equation
[CH3:1][C:2]1[C:6]([NH:7][C:8]2[CH:9]=[N:10][CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[CH:15]=3)[CH:13]=2)=[C:5]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][C:30]([C:33]4([C:36]([OH:38])=O)[CH2:35][CH2:34]4)=[CH:29][CH:28]=3)=[CH:23][CH:22]=2)[O:4][N:3]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[CH3:50][S:51]([NH2:54])(=[O:53])=[O:52].CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[CH3:1][C:2]1[C:6]([NH:7][C:8]2[CH:9]=[N:10][CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[CH:15]=3)[CH:13]=2)=[C:5]([C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:32]=[CH:31][C:30]([C:33]4([C:36]([NH:54][S:51]([CH3:50])(=[O:53])=[O:52])=[O:38])[CH2:34][CH2:35]4)=[CH:29][CH:28]=3)=[CH:25][CH:26]=2)[O:4][N:3]=1

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 72879MethanesulfonamideHCID 81531DiisopropylethylamineHCID 66558561HCID 66558561, compound

Product 1

HCID 70817168N-(1-{4'-[3-Methyl-4-(5-(3-methyl-phenyl)-pyridin-3-ylamino)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarbonyl)-methanesulfonamide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 1-(4′-{3-methyl-4-[5-(3-methyl-phenyl)-pyridin-3-ylamino]-isoxazol-5-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid (0.050 g, 0.1 mmol) in DCM (1 mL) at RT was added DMF (1 μL, 0.01 mmol) and oxalyl chloride (17 μL, 0.15 mmol). After 1 hr, the mixture was concentrated to dryness and re-dissolved in DCM (1 mL). To this solution was added methanesulfonamide (0.014 g, 0.15 mmol), DIEA (60 μL, 0.35 mmol), and DMAP (0.001 g). The resulting mixture was stirred for 5 min, then diluted with EtOAc (20 mL) and extracted with H2O (2×10 mL). The combined aqueous layers were back-extracted with EtOAc (10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. The crude residue was purified on reverse-phase preparative HPLC to afford the title compound.

Workup

  1. concentrationthe mixture was concentrated to dryness
  2. dissolutionre-dissolved in DCM (1 mL)
  3. extractionextracted with H2O (2×10 mL)
  4. extractionThe combined aqueous layers were back-extracted with EtOAc (10 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified on reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-739c4444d79e41469b0f3cca7abfdb16
Source dataset
uspto-grants-2013_09
Patent number
US08541587B2

Reaction notes

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