Potassium Carbonate → (R)-2-(5-cyano-6-(3-methylisothiazol-5-ylamino)pyrazin-2-ylamino)butanamide

HRID 332825Notes

Reaction equation

HRID 332825 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([CH2:13][CH3:14])[C:10]([NH2:12])=[O:11])[CH:5]=[N:4][C:3]=1[C:15]#[N:16].Cl.[CH3:18][C:19]1[CH:23]=[C:22]([NH2:24])[S:21][N:20]=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:15]([C:3]1[N:4]=[CH:5][C:6]([NH:8][C@H:9]([CH2:13][CH3:14])[C:10]([NH2:12])=[O:11])=[N:7][C:2]=1[NH:24][C:22]1[S:21][N:20]=[C:19]([CH3:18])[CH:23]=1)#[N:16]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 86685581(R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)butanamide

Product 1

HCID 86685617(R)-2-(5-cyano-6-(3-methylisothiazol-5-ylamino)pyrazin-2-ylamino)butanamideYield 89.1%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)butanamide (90 mg, 0.375 mmol), 3-methylisothiazol-5-amine hydrochloride (70 mg, 0.464 mmol), K2CO3 (130 mg, 0.942 mmol), BINAP (30 mg, 0.048 mmol) and Pd(OAc)2 (15 mg, 0.066 mmol) in dioxane (2 mL) was degassed with Ar, then was stirred at 110 C for 20 h. EtOAc and H2O were added. Organic phase was separated, dried over Na2SO4, concentrated in vacuo to give (R)-2-(5-cyano-6-(3-methylisothiazol-5-ylamino)pyrazin-2-ylamino)butanamide (106 mg).

Workup

  1. customwas degassed with Ar
  2. additionEtOAc and H2O were added
  3. customOrganic phase was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4f1c7fb3f021441482718c1f2ef6ea31
Source dataset
uspto-grants-2014_11
Patent number
US08877760B2

Reaction notes

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