Water → HCID 49821056, compound

HRID 1897820Notes

Reaction equation

HRID 1897820 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[C:14]([C:19]#[N:20])[CH:13]=[CH:12]3)O1.Br[C:23]1[CH:24]=[C:25]([CH:29]([CH:36]2[CH2:38][CH2:37]2)[NH:30][S:31]([CH2:34][CH3:35])(=[O:33])=[O:32])[CH:26]=[N:27][CH:28]=1.C(=O)([O-])[O-].[Na+].[Na+].O.C(Cl)Cl>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].CN(C=O)C>[C:19]([C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[C:9]([C:23]1[CH:24]=[C:25]([CH:29]([CH:36]3[CH2:38][CH2:37]3)[NH:30][S:31]([CH2:34][CH3:35])(=[O:32])=[O:33])[CH:26]=[N:27][CH:28]=1)[CH:18]=[CH:17]2)#[N:20]

Participants

8

Reactant 5

HCID 962WaterHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 59578386N-((5-bromopyridin-3-yl)(cyclopropyl)methyl)ethanesulfonamideHCID 667878886-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthonitrile

Product 1

HCID 49821056HCID 49821056, compoundYield 27.1%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthonitrile (335 mg, 1.200 mmol), N-((5-bromopyridin-3-yl)(cyclopropyl)methyl)ethanesulfonamide (319 mg, 1 mmol), sodium carbonate (2 M) in water (1.000 mL, 2.000 mmol), PdCl2(dppf).CH2Cl2 adduct (40.8 mg, 0.050 mmol) in DMF (4.000 mL) was heated to 100° C. for 30 min. The mixture was quenched with saturated aqueous NaHCO3 and extracted with EtOAc two times, dried over magnesium sulfate, filtered, concentrated. The residue was purified via Biotage (10-100% EtOAc/heptane; SNAP25 column) giving the title compound (106 mg, 27%) as a white solid 1H NMR (400 MHz, MeOD) δ ppm 0.43-0.55 (m, 1H) 0.56-0.69 (m, 2H) 0.69-0.83 (m, 1H) 1.28 (t, J=7.36 Hz, 3H) 1.25-1.39 (m, 1H) 2.82-3.10 (m, 2H) 3.95 (d, J=9.09 Hz, 1H) 7.73 (dd, J=8.53, 1.45 Hz, 1H) 8.00 (dd, J=8.59, 1.71 Hz, 1H) 8.15 (s, 1H) 8.17 (s, 1H) 8.28-8.35 (m, 2H) 8.44 (s, 1H) 8.65 (d, J=2.02 Hz, 1H) 8.90 (d, J=2.08 Hz, 1H). LC-MS (M+1) 392.2. Enantiomers were separated by chiral HPLC (IA 21×250 mm, flow rate: 14 mL/min, 60% heptane 20% methanol 20% ethanol) and yielded enantiomer −1 with retention time (14.10 min) and enantiomer-2 with retention time (18.16 min).

Workup

  1. customThe mixture was quenched with saturated aqueous NaHCO3
  2. extractionextracted with EtOAc two times
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified via Biotage (10-100% EtOAc/heptane; SNAP25 column)

Sources & evidence

ORD record
ord-9040d0cc97014639b8828da2cb5e21b8
Source dataset
uspto-grants-2013_08
Patent number
US08519142B2

Reaction notes

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