Toluene → HCID 178430464, compound

HRID 1944757Notes

Reaction equation

HRID 1944757 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)=[C:25]([Cl:30])[CH:24]=3)(=[O:22])=[O:21])[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].C[C:38]1[CH:43]=[C:42](B(O)O)[CH:41]=[CH:40][N:39]=1.[C:47]1(C)C=CC=CC=1>CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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]=[CH:38][N:39]=[CH:40][C:41]=4[CH3:47])=[C:25]([Cl:30])[CH:24]=3)(=[O:22])=[O:21])[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 41926642-Methylpyridine-4-boronic acidHCID 178462120HCID 178462120, compound

Product 1

HCID 178430464HCID 178430464, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Procedure

Trans-4-(4-Bromo-3-chloro-benzenesulfonylamino)-cyclohexanecarboxylic acid [(R)-1-(4-fluoro-phenyl)-ethyl]-amide (Example 155, 100 mg, 0.193 mmol), Pd tetrakis (45 mg, 0.039 mmol), Na2CO3 (52 mg, 4.83 mmol) and 2-methyl-4-pyridine boronic acid (34 mg, 0.251 mmol) was dissolved in EtOH (4 ml) and toluene (4 ml) under N2 and the mixture was refluxed overnight. LCMS indicated that the reaction was complete, and it was concentrated in vacuo. then taken up in EtOAc and washed with H2O (×2). The organic layer was concentrated in vacuo, and the crude material was purified via column chromatography using a biotage SP1 25+S column with a gradient 80%-100% EtOAc in heptane. Product fractions were combined and repurified on prep-HPLC (150 mm, C8 luna, 15-20 min run, 10%-100% MeCN in water containing 0.1% TFA), then lyophilized to yield the title compound as a white solid (27 mg, 22%). MS MH+ 530.1

Workup

  1. concentrationit was concentrated in vacuo
  2. washwashed with H2O (×2)
  3. concentrationThe organic layer was concentrated in vacuo
  4. customthe crude material was purified via column chromatography
  5. customrepurified on prep-HPLC (150 mm, C8 luna, 15-20 min run, 10%-100% MeCN in water containing 0.1% TFA)

Sources & evidence

ORD record
ord-de615e51e4834c20a49347d9ded7e86f
Source dataset
uspto-grants-2013_03
Patent number
US08394858B2

Reaction notes

Loading…