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 386834노트

반응식

HRID 386834 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 μmol), 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-65fd147746234af99492ca3757bffc07
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372870B2

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