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

HRID 84883
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HRID 84883 반응식
Br[C:2]1[C:3]([C:21]#[N:22])=[CH:4][C:5]([F:20])=[C:6]([NH:8][C@H:9]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[C:10]([NH2:12])=[O:11])[CH:7]=1.Cl.[NH2:24][C:25]1[S:29][N:28]=[C:27]([CH3:30])[CH:26]=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:21]([C:3]1[C:2]([NH:24][C:25]2[S:29][N:28]=[C:27]([CH3:30])[CH:26]=2)=[CH:7][C:6]([NH:8][C@H:9]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[C:10]([NH2:12])=[O:11])=[C:5]([F:20])[CH:4]=1)#[N:22]
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참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67509302(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-(pyridin-2-yl)propanamide

생성물 1

HCID 67508724(R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-(pyridin-2-yl)propanamide수율 38.9%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

실험 절차

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-(pyridin-2-yl)propanamide (125 mg, 0.344 mmol), 5-amino-3-methylisothiazole hydrochloride (80 mg, 0.531 mmol), K2CO3 (220 mg, 1.59 mmol), BINAP (40 mg, 0.064 mmol) and Pd(OAc)2 (30 mg, 0.133 mmol) in dioxane (3 mL) was degassed with argon, then was stirred at 120 C for 18 h. The mixture was concentrated in vacuo. The residue was purified by HPLC to give (R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-(pyridin-2-yl)propanamide (53 mg).

후처리

  1. customwas degassed with argon
  2. concentrationThe mixture was concentrated in vacuo
  3. customThe residue was purified by HPLC

출처 및 근거

ORD 기록
ord-fe30c4ca657246f9a98c34efa9b818f8
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08846928B2

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