Potassium Carbonate → 2-(3-Methylisothiazol-5-ylamino)-4-(2-oxoazepan-3-ylamino)benzonitrile

HRID 2201106Notes

Reaction equation

HRID 2201106 reaction equation
Br[C:2]1[CH:9]=[C:8]([NH:10][CH:11]2[CH2:17][CH2:16][CH2:15][CH2:14][NH:13][C:12]2=[O:18])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Cl.[NH2:20][C:21]1[S:25][N:24]=[C:23]([CH3:26])[CH:22]=1.C([O-])([O-])=O.[K+].[K+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:26][C:23]1[CH:22]=[C:21]([NH:20][C:2]2[CH:9]=[C:8]([NH:10][CH:11]3[CH2:17][CH2:16][CH2:15][CH2:14][NH:13][C:12]3=[O:18])[CH:7]=[CH:6][C:3]=2[C:4]#[N:5])[S:25][N:24]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 675087722-Bromo-4-(2-oxoazepan-3-ylamino)benzonitrile

Product 1

HCID 675082872-(3-Methylisothiazol-5-ylamino)-4-(2-oxoazepan-3-ylamino)benzonitrileYield 159.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-bromo-4-(2-oxoazepan-3-ylamino)benzonitrile (81 mg, 0.263 mmol), 5-amino-3-methylisothiazole hydrochloride (63 mg, 0.418 mmol), K2CO3 (120 mg, 0.869 mmol), BINAP (40 mg, 0.064 mmol) and Pd(OAc)2 (20 mg, 0.089 mmol) in dioxane (3 mL) was degassed with argon, then was stirred at 120 C for 18 h. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo to give 2-(3-methylisothiazol-5-ylamino)-4-(2-oxoazepan-3-ylamino)benzonitrile (143 mg)

Workup

  1. customwas degassed with argon
  2. additionWater and EtOAc were added
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7ecb1d0f0a3c422e9f7b4339308e928d
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Reaction notes

Loading…