Potassium Carbonate → HCID 67509932, compound

HRID 2201130Notes

Reaction equation

HRID 2201130 reaction equation
Br[C:2]1[C:3]([C:27]#[N:28])=[CH:4][C:5]([F:26])=[C:6]([NH:8][C@H:9]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[C:10]([NH2:12])=[O:11])[CH:7]=1.Cl.[NH2:30][C:31]1[S:35][N:34]=[C:33]([CH3:36])[CH:32]=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.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:27]([C:3]1[C:2]([NH:30][C:31]2[S:35][N:34]=[C:33]([CH3:36])[CH:32]=2)=[CH:7][C:6]([NH:8][C@H:9]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[C:10]([NH2:12])=[O:11])=[C:5]([F:26])[CH:4]=1)#[N:28]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67508174(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-(4-(pyridin-4-yl)phenyl)propanamide

Product 1

HCID 67509932HCID 67509932, compoundYield 18.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-(4-(pyridin-4-yl)phenyl)propanamide (62 mg, 0.14 mmol), 5-amino-3-methylisothiazole hydrochloride (35 mg, 0.23 mmol), K2CO3 (65 mg, 0.47 mmol), BINAP (25 mg, 0.040 mmol) and Pd(OAc)2 (15 mg, 0.066 mmol) in dioxane (2 mL) and water (0.1 mL) was degassed with argon, then was stirred at 120 C for 18 h. The mixture was purified by HPLC to give (R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-(4-(pyridin-4-yl)phenyl)propanamide (12 mg).

Workup

  1. customwas degassed with argon
  2. customThe mixture was purified by HPLC

Sources & evidence

ORD record
ord-1e42bc91fdf84759be319ac0435a1f9d
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Reaction notes

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