Dichloromethane → HCID 178430475, compound

HRID 1944755Notes

Reaction equation

HRID 1944755 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C:11]([C@H:13]2[CH2:18][CH2:17][C@H:16]([NH:19][S:20]([C:23]3[CH:28]=[CH:27][C:26](Br)=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+].[CH3:39][C:40]1[CH:41]=[C:42](B(O)O)[CH:43]=[N:44][CH:45]=1>CN(C=O)C.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C:11]([C@H:13]2[CH2:18][CH2:17][C@H:16]([NH:19][S:20]([C:23]3[CH:28]=[CH:27][C:26]([C:42]4[CH:43]=[N:44][CH:45]=[C:40]([CH3:39])[CH:41]=4)=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27627085-Methylpyridine-3-boronic acidHCID 178462119HCID 178462119, compound

Product 1

HCID 178430475HCID 178430475, compoundYield 43.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Trans-4-(4-Bromo-benzenesulfonylamino)-cyclohexanecarboxylic acid [(R)-1-(4-fluoro-phenyl)-ethyl]-amide (Example 115, 100 mg, 0.206 mmol), Pd(dppf)Cl2.DCM (34 mg, 0.04 mmol), 2M Na2CO3 (1 ml, 2.06 mmol) and 5-methyl-3-pyridine boronic acid (51 mg, 0.37 mmol) were dissolved in DMF (1-2 ml) under N2. The reaction mixture was microwaved at 160° C. for 20 min., after which LCMS indicated that the reaction was complete. The mixture was diluted with EtOAc and washed with H2O (×2). The organic layer was concentrated in vacuo, and the crude material purified via column chromatography using a biotage SP1 25+S column with a gradient of 80-100% EtOAc in heptane. Product fractions combined and concentrated to give the title compound as a white solid (44 mg, 43%). MS MH+ 496.1

Workup

  1. customThe reaction mixture was microwaved at 160° C. for 20 min.
  2. washwashed with H2O (×2)
  3. concentrationThe organic layer was concentrated in vacuo
  4. customthe crude material purified via column chromatography
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-189312bd3d904128a597e6bf2716f0b8
Source dataset
uspto-grants-2013_03
Patent number
US08394858B2

Reaction notes

Loading…