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

HRID 84853노트

반응식

HRID 84853 반응식
Br[C:2]1[C:3]([C:17]#[N:18])=[CH:4][C:5]([F:16])=[C:6]([NH:8][C@H:9]([CH2:13][O:14][CH3:15])[C:10]([NH2:12])=[O:11])[CH:7]=1.Cl.[NH2:20][C:21]1[S:25][N:24]=[C:23]([CH3:26])[CH:22]=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:17]([C:3]1[C:2]([NH:20][C:21]2[S:25][N:24]=[C:23]([CH3:26])[CH:22]=2)=[CH:7][C:6]([NH:8][C@H:9]([CH2:13][O:14][CH3:15])[C:10]([NH2:12])=[O:11])=[C:5]([F:16])[CH:4]=1)#[N:18]

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67508869(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-methoxypropanamide

생성물 1

HCID 67508557(R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-methoxypropanamide수율 27.9%

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-methoxypropanamide (52 mg, 0.164 mmol), 5-amino-3-methylisothiazole hydrochloride (40 mg, 0.265 mmol), K2CO3 (110 mg, 0.797 mmol), BINAP (30 mg, 0.048 mmol) and Pd(OAc)2 (25 mg, 0.111 mmol) in dioxane (2 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-methoxypropanamide (16 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-235e5755624f4b34a3f780f8c5c2798b
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846928B2

반응 노트

불러오는 중…