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

HRID 2201103
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HRID 2201103 반응식
Br[C:2]1[C:3]([C:17]#[N:18])=[CH:4][C:5]([F:16])=[C:6]([NH:8][C@H:9]([CH:13]2[CH2:15][CH2:14]2)[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]([CH:13]2[CH2:15][CH2:14]2)[C:10]([NH2:12])=[O:11])=[C:5]([F:16])[CH:4]=1)#[N:18]
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참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 27239183-Methylisothiazol-5-ylamine hydrochlorideHCID 67509451(R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-2-cyclopropylacetamide

생성물 1

HCID 67508988(R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-2-cyclopropylacetamide수율 39.6%

시약·촉매·용매

2
HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

실험 절차

A mixture of (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-2-cyclopropylacetamide (87 mg, 0.278 mmol), 5-amino-3-methylisothiazole hydrochloride (63 mg, 0.418 mmol), K2CO3 (120 mg, 0.869 mmol), BINAP (40 mg, 0.064 mmol) and Pd(OAc)2 (20 mg, 0.089 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)-2-cyclopropylacetamide (38 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-71cd7479abc24dd5934cfb07c656033b
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09359375B2

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