Dimethylformamide → 5-[3-[4-({4-[(1,1-Dioxidothiomorpholin-4-yl)methyl]benzyl}amino)-1,2,5-oxadiazol-3-yl]-5-oxo-1,2,4-oxadiazol-4-yl]-2-fluorobenzonitrile trifluoroacetate

HRID 82731노트

반응식

HRID 82731 반응식
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].Br[C:9]1[CH:10]=[C:11]([N:16]2[C:20](=[O:21])[O:19][N:18]=[C:17]2[C:22]2[C:26]([NH:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([CH2:35][N:36]4[CH2:41][CH2:40][S:39](=[O:43])(=[O:42])[CH2:38][CH2:37]4)=[CH:31][CH:30]=3)=[N:25][O:24][N:23]=2)[CH:12]=[CH:13][C:14]=1[F:15].[CH3:44][N:45](C)C=O>C(#N)C.O.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[O:42]=[S:39]1(=[O:43])[CH2:40][CH2:41][N:36]([CH2:35][C:32]2[CH:33]=[CH:34][C:29]([CH2:28][NH:27][C:26]3[C:22]([C:17]4[N:16]([C:11]5[CH:12]=[CH:13][C:14]([F:15])=[C:9]([CH:10]=5)[C:44]#[N:45])[C:20](=[O:21])[O:19][N:18]=4)=[N:23][O:24][N:25]=3)=[CH:30][CH:31]=2)[CH2:37][CH2:38]1

참가 물질

6

반응물 2

HCID 6228DimethylformamideHCID 674350044-(3-Bromo-4-fluorophenyl)-3-[4-({4-[(1,1-dioxidothiomorpholin-4-yl)methyl]benzyl}amino)-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-5(4H)-one trifluoroacetate

생성물 1

HCID 674381925-[3-[4-({4-[(1,1-Dioxidothiomorpholin-4-yl)methyl]benzyl}amino)-1,2,5-oxadiazol-3-yl]-5-oxo-1,2,4-oxadiazol-4-yl]-2-fluorobenzonitrile trifluoroacetate

시약·촉매·용매 3

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 18373917Acetonitrile--water (1/1)용매

실험 절차

A solution of 4-(3-bromo-4-fluorophenyl)-3-[4-({4-[(1,1-dioxidothiomorpholin-4-yl)methyl]benzyl}amino)-1,2,5-oxadiazol-3-yl]-1,2,4-oxadiazol-5(4H)-one trifluoroacetate (10 mg, 14 μmol), zinc cyanide (5 mg, 43 mmol), and tetrakis(triphenylphosphine)palladium(0) (8 mg, 7 μmol) in N,N-dimethylformamide (0.25 mL) was heated in the microwave at 150° C. for 5 min. The reaction mixture was diluted with 3:1 acetonitrile/water (2 mL), filtered, and purified by preparative LCMS to give the intermediate 5-[3-[4-({4-[(1,1-dioxidothiomorpholin-4-yl)methyl]benzyl}amino)-1,2,5-oxadiazol-3-yl]-5-oxo-1,2,4-oxadiazol-4(5H)-yl]-2-fluorobenzonitrile trifluoroacetate. This material was diluted with ethanol (1 mL), treated with 2.0 M sodium hydroxide in water (0.1 mL), and stirred for 45 min. The reaction mixture was quenched with acetic acid (50 μL, 0.9 mmol), filtered, and purified by preparative LCMS to give the desired product (1 mg, 11%). LCMS for C22H23FN7O4S (M+H)+: m/z=500.0.

후처리

  1. filtrationfiltered
  2. custompurified by preparative LCMS

출처 및 근거

ORD 기록
ord-1f64f2404976453592d1c2dcb6696a85
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846726B2

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