Potassium Carbonate → (R)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)-3-(1H-indol-3-yl)propanamide

HRID 2201111Notes

Reaction equation

HRID 2201111 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)[C:12]([NH2:14])=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Cl.[NH2:26][C:27]1[S:31][N:30]=[C:29]([CH3:32])[CH:28]=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]>[C:8]([C:7]1[CH:6]=[CH:5][C:4]([NH:10][C@H:11]([CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)[C:12]([NH2:14])=[O:13])=[CH:3][C:2]=1[NH:26][C:27]1[S:31][N:30]=[C:29]([CH3:32])[CH:28]=1)#[N:9]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67514877(R)-2-(3-bromo-4-cyanophenylamino)-3-(1H-indol-3-yl)propanamide

Product 1

HCID 67515880(R)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)-3-(1H-indol-3-yl)propanamideYield 96%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of (R)-2-(3-bromo-4-cyanophenylamino)-3-(1H-indol-3-yl)propanamide (96 mg, 0.250 mmol), 5-amino-3-methylisothiazole hydrochloride (60 mg, 0.398 mmol), K2CO3 (120 mg, 0.869 mmol), BINAP (40 mg, 0.064 mmol) and Pd(OAc)2 (20 mg, 0.089 mmol) in dioxane (2 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 (R)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)-3-(1H-indol-3-yl)propanamide (100 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-0773388fdf464dfd970cdd3233eaf15f
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Reaction notes

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