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

HRID 2201073노트

반응식

HRID 2201073 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]C=CC=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.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].CCOC(C)=O.O>[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][CH:14]2[CH2:19][CH2:18]2)[C:10]([NH2:12])=[O:11])=[C:5]([F:20])[CH:4]=1)#[N:22]

참가 물질

9

반응물 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67508222(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-phenylpropanamide

생성물 1

HCID 67508416(R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-cyclopropylpropanamide

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매2회HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-phenylpropanamide (362 mg, 1.00 mmol), 5-amino-3-methylisothiazole hydrochloride (166 mg, 1.10 mmol), BINAP (70 mg, 0.112 mmol), Pd(OAc)2 (35 mg, 0.156 mmol) and K2CO3 (430 mg, 3.11 mmol) in dioxane (5 mL) was degassed with Ar, then was stirred at 120 C for 18 h. More Pd(OAc)2 (35 mg, 0.156 mmol) was added. The mixture was stirred at 120 C for another 18 h. Water and EtOAc were added. After being filtered, the filtrate was washed with water, dried over Na2SO4, concentrated in vacuo to give (R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-cyclopropylpropanamide as a crude residue.

후처리

  1. customwas degassed with Ar
  2. stirringThe mixture was stirred at 120 C for another 18 h
  3. filtrationAfter being filtered
  4. washthe filtrate was washed with water
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-9f87555f511a47ea894e6d8c755cf6b0
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09359375B2

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