Dichloromethane → N-(cyclopropyl(5-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)pyridin-3-yl)methyl)ethanesulfonamide

HRID 1253939Notes

Reaction equation

HRID 1253939 reaction equation
[CH3:1][N:2]1[C:6]2[CH:7]=[C:8](B3OC(C)(C)C(C)(C)O3)[CH:9]=[CH:10][C:5]=2[O:4][C:3]1=[O:20].Br[C:22]1[CH:23]=[C:24]([CH:28]([CH:35]2[CH2:37][CH2:36]2)[NH:29][S:30]([CH2:33][CH3:34])(=[O:32])=[O:31])[CH:25]=[N:26][CH:27]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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]>[CH:35]1([CH:28]([C:24]2[CH:25]=[N:26][CH:27]=[C:22]([C:8]3[CH:9]=[CH:10][C:5]4[O:4][C:3](=[O:20])[N:2]([CH3:1])[C:6]=4[CH:7]=3)[CH:23]=2)[NH:29][S:30]([CH2:33][CH3:34])(=[O:32])=[O:31])[CH2:37][CH2:36]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 595350693-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(3H)-benzoxazoloneHCID 59578386N-((5-bromopyridin-3-yl)(cyclopropyl)methyl)ethanesulfonamide

Product 1

HCID 49802306N-(cyclopropyl(5-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)pyridin-3-yl)methyl)ethanesulfonamideYield 54%

Reagents, catalysts & solvents 2

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

Procedure

The mixture of 3-Methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3H-benzooxazol-2-one (115 mg, 0.42 mmol), N-((5-bromopyridin-3-yl)(cyclopropyl)methyl)ethane-sulfonamide (133 mg, 0.42 mmol), PdCl2(dppf).CH2Cl2 (34 mg, 0.04 mmol) and Na2CO3 (2 M in water, 0.42 mL, 0.83 mmol) in DMF (6 mL) was heated at 100° C. for 3 h. After concentration, the residue was diluted with DCM, and subsequently filtered to remove insoluble solid. The filtrate was concentrated and purified by flash column (MeOH—CH2Cl2, v/v, 0-4%) to give N-(cyclopropyl(5-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)pyridin-3-yl)methyl)ethanesulfonamide (87 mg, 54%); ESI-MS m/z: 388 [M+1]+, Retention time 1.35 min; 1H-NMR (MeOD, 400 MHz) δ 8.80 (1H, d, J=2.0 Hz), 8.62 (1H, d, J=2.0 Hz), 8.20 (1H, t, J=2.0 Hz), 7.54 (1H, d, J=2.4 Hz), 7.50 (1H, dd, J=8.4, 24 Hz), 7.42 (1H, d, J=84 Hz), 3.95 (1H, d, J=8.8 Hz), 3.52 (3H, s), 3.05-2.92 (2H, m), 1.36-1.30 (1H, m), 1.30 (1H, t, J=7.2 Hz), 0.81-0.77 (1H, m), 0.66-0.62 (2H, m), 0.55-0.47 (1H, m)

Workup

  1. concentrationAfter concentration
  2. additionthe residue was diluted with DCM
  3. filtrationsubsequently filtered
  4. customto remove insoluble solid
  5. concentrationThe filtrate was concentrated
  6. custompurified by flash column (MeOH—CH2Cl2, v/v, 0-4%)

Sources & evidence

ORD record
ord-97ee6e5e4430414fa8acbfaff4e108cd
Source dataset
uspto-grants-2013_06
Patent number
US08455522B2

Reaction notes

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