Tri-o-tolylphosphine → 1-(2,3-Difluoro-4-hydroxy-phenyl)-2-(2-methyl-allyl)-1H-indole-3-carbonitrile

HRID 383470노트

반응식

HRID 383470 반응식
Br[C:2]1[N:3]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[C:15]([F:20])[C:14]=2[F:21])[C:4]2[C:9]([C:10]=1[C:11]#[N:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.[CH2:22]([Sn](CCCC)(CCCC)CCCC)[C:23](=[CH2:25])[CH3:24].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:21][C:14]1[C:15]([F:20])=[C:16]([OH:19])[CH:17]=[CH:18][C:13]=1[N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]([C:11]#[N:12])=[C:2]1[CH2:24][C:23]([CH3:25])=[CH2:22]

참가 물질

6

반응물 3

HCID 80271Tri-o-tolylphosphineHCID 11013379Methallyltri-n-butyltinHCID 444648052-bromo-1-(2,3-difluoro-4-hydroxyphenyl)-1H-indole-3-carbonitrile

생성물 1

HCID 444669351-(2,3-Difluoro-4-hydroxy-phenyl)-2-(2-methyl-allyl)-1H-indole-3-carbonitrile

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

A mixture of 2-bromo-1-(2,3-difluoro-4-hydroxyphenyl)-1H-indole-3-carbonitrile (Example 103), methallyltri-n-butyltin (2 eq), Pd2(dba)3 (0.05%) and tri(o-tolyl)phosphine (20%) was dissolved in DMF, degassed with N2 and heated at 80° C. over night. The reaction mixture was quenched by addition of sat. NH4Cl, diluted with EtOAc, and washed with brine and then dried over Na2SO4. The residue was subjected to reversed phase preparative HPLC. Appropriate fractions were combined and evaporated, and identified by 1H NMR. ES/MS m/z: 289.11 (M+H), 287.15 (M−H); 1H NMR (chloroform-d, 500 MHz): 7.76 (m, 1H), 7.28 (m, 1H), 7.23 (m, 1H), 7.17 (m, 2H), 7.13 (m, 1H), 6.98 (m, 2H), 5.86 (m, 1H), 1.98 (d, 3H, J=1.3 Hz) and 1.89 (d, 3H, J=1.2 Hz).

후처리

  1. customdegassed with N2
  2. customThe reaction mixture was quenched by addition of sat. NH4Cl
  3. additiondiluted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated

출처 및 근거

ORD 기록
ord-5e52e7028b50493ba9fe4dda12e2a493
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367665B2

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