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

HRID 383470Notes

Reaction equation

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]

Participants

Conditions

Temperature: 80 °C

Procedure

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).

Workup

customdegassed with N2
customThe reaction mixture was quenched by addition of sat. NH4Cl
additiondiluted with EtOAc
washwashed with brine
dry with materialdried over Na2SO4
customevaporated

Sources & evidence

ORD record: ord-5e52e7028b50493ba9fe4dda12e2a493
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367665B2

Reaction notes

Loading…