Pyrazole → HCID 178462125, compound

HRID 1944758Notes

Reaction equation

HRID 1944758 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:24]=[N:25][C:26](Cl)=[CH:27][CH:28]=3)(=[O:22])=[O:21])[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1.[NH:30]1[CH:34]=[CH:33][CH:32]=[N:31]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(O)(C)(C)C.C(Cl)Cl.CC#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[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:24]=[N:25][C:26]([N:30]4[CH:34]=[CH:33][CH:32]=[N:31]4)=[CH:27][CH:28]=3)(=[O:22])=[O:21])[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 1048PyrazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 178462123HCID 178462123, compound

Product 1

HCID 178462125HCID 178462125, compoundYield 14.1%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Procedure

Trans-4-(6-Chloro-pyridine-3-sulfonylamino)-cyclohexanecarboxylic acid [(R)-1-(4-fluoro-phenyl)-ethyl]-amide (Example 114, 100 mg, 0.225 mmol), pyrazole (70 mg, 0.91 mmol), Pd2(dba)3 (25 mg, 0.025 mmol), Xantphos (20 mg, 0.05 mmol), sodium tert-butoxide (108 mg, 1.125 mmol) were dissolved in toluene (1 ml) and tert-butanol (3 ml). The reaction mixture was microwaved at 160° C. for 5 min., after which LCMS indicated that the reaction was complete. The reaction was diluted with DCM and MeCN and filtered through a syringe, the concentrated in vacuo to a yellow oil. The crude material was purified via reverse phase chromatography and lyophilized to yield the title compound as a white solid (15 mg, 14%). [M+H]=472.08

Workup

  1. customThe reaction mixture was microwaved at 160° C. for 5 min.
  2. filtrationfiltered through a syringe
  3. concentrationthe concentrated in vacuo to a yellow oil
  4. customThe crude material was purified via reverse phase chromatography

Sources & evidence

ORD record
ord-56f1fa107ca44d5c8a8b35d378841d22
Source dataset
uspto-grants-2013_03
Patent number
US08394858B2

Reaction notes

Loading…