Potassium Carbonate → (R)-3-(benzyloxy)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)propanamide

HRID 2201051

Reaction equation

HRID 2201051 reaction equation
[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[C:17](Br)[CH:16]=1)[C:11]([NH2:13])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:25][C:26]1[S:30][N:29]=[C:28]([CH3:31])[CH:27]=1.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.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[C:17]([NH:25][C:26]2[S:30][N:29]=[C:28]([CH3:31])[CH:27]=2)[CH:16]=1)[C:11]([NH2:13])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67509048(R)-3-(benzyloxy)-2-(3-bromo-4-cyanophenylamino)propanamide

Product 1

HCID 67508575(R)-3-(benzyloxy)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)propanamide

Reagents, catalysts & solvents 2

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

Procedure

A mixture of (R)-3-(benzyloxy)-2-(3-bromo-4-cyanophenylamino)propanamide (66 mg, 0.176 mmol), 5-amino-3-methylisothiazole hydrochloride (35 mg, 0.232 mmol), BINAP (20 mg, 0.032 mmol), Pd(OAc)2 (15 mg, 0.066 mmol) and K2CO3 (100 mg, 0.724 mmol) in dioxane (2 mL) was degassed with Ar, then was stirred at 120 C for 18 h. Water and EtOAc were added. After being filtered, the organic phase was separated, dried over Na2SO4, concentrated in vacuo to give (R)-3-(benzyloxy)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)propanamide as a crude residue (73 mg).

Workup

  1. customwas degassed with Ar
  2. additionWater and EtOAc were added
  3. filtrationAfter being filtered
  4. customthe organic phase was separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b6d2c73669a04b86b1fb98b77f1f984e
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Linked notes

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