Dimethylamine → HCID 178494218, compound

HRID 1944753Notes

Reaction equation

HRID 1944753 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]([O:30][CH3:31])=[C:27](Br)[CH:28]=3)(=[O:22])=[O:21])[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1.[CH3:32][NH:33][CH3:34].C1COCC1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>CN(C=O)C.O.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]>[CH3:32][N:33]([CH3:34])[C:27]1[CH:28]=[C:23]([S:20]([NH:19][C@H:16]2[CH2:17][CH2:18][C@H:13]([C:11]([NH:10][C@@H:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[CH3:9])=[O:12])[CH2:14][CH2:15]2)(=[O:22])=[O:21])[CH:24]=[N:25][C:26]=1[O:30][CH3:31]

Participants

9

Reactant 5

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 178494217HCID 178494217, compound

Product 1

HCID 178494218HCID 178494218, compoundYield 28%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Trans-4-(5-Bromo-6-methoxy-pyridine-3-sulfonylamino)-cyclohexanecarboxylic acid [(R)-1-(4-fluoro-phenyl)-ethyl]-amide (Example 223, 65 mg, 0.126 mmol), dimethylamine in THF (2M, 630 ul, 1.26 mmol), Pd2(dba)3 (12 mg, 0.013 mmol), X-phos (6 mg, 0.013 mmol), sodium tert-butoxide (61 mg, 0.63 mmol) were dissolved in DMF (2 ml). The reaction mixture was microwaved at 180° C. for 15 min., after which LCMS indicated the reaction was complete. The mixture was diluted with H2O and extracted with EtOAc (×3). The combined organic layers were concentrated in vacuo to a yellow oil which was purified via column chromatography using a biotage SP1, 25+M column, with 80% EtOAc in heptane as an isocratic gradient. Product containing fractions were concentrated in vacuo and repurified via reverse phase chromatography on prep-HPLC (150 mm, C8 luna, 15-20 min run, 10%-100% MeCN in water containing 0.1% TFA). Product containing fractions were collected and lyophilized to yield the title compound as a white solid (25.3 mg, 28%). MS MH+ 479.1

Workup

  1. customThe reaction mixture was microwaved at 180° C. for 15 min.
  2. extractionextracted with EtOAc (×3)
  3. concentrationThe combined organic layers were concentrated in vacuo to a yellow oil which
  4. customwas purified via column chromatography
  5. additionProduct containing fractions
  6. concentrationwere concentrated in vacuo
  7. customrepurified via reverse phase chromatography on prep-HPLC (150 mm, C8 luna, 15-20 min run, 10%-100% MeCN in water containing 0.1% TFA)
  8. additionProduct containing fractions
  9. customwere collected

Sources & evidence

ORD record
ord-d0c955eeb54340a191be6e27c641b788
Source dataset
uspto-grants-2013_03
Patent number
US08394858B2

Reaction notes

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