2,6-Dimethylphenylboronic acid → 3-{4-[5-(2,6-Dimethylphenyl)-thiophen-2-yl]-pyrimidin-2-ylamino}-phenylethanol

HRID 1012178Notes

Reaction equation

HRID 1012178 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:15]=[C:16]([CH:20]([OH:22])[CH3:21])[CH:17]=[CH:18][CH:19]=3)[N:8]=2)=[CH:4][CH:3]=1.[CH3:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[C:25]=1B(O)O>CC(N(C)C)=O.C([O-])([O-])=O.[Na+].[Na+].CS(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[C:25]=1[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:15]=[C:16]([CH:20]([OH:22])[CH3:21])[CH:17]=[CH:18][CH:19]=3)[N:8]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 2

HCID 5833222,6-Dimethylphenylboronic acidHCID 16666603HCID 16666603, compound

Product 1

HCID 166666463-{4-[5-(2,6-Dimethylphenyl)-thiophen-2-yl]-pyrimidin-2-ylamino}-phenylethanolYield 30.5%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 10340Sodium CarbonateSolventHCID 31374DimethylacetamideSolvent

Procedure

1-{3-[4-(5-Bromothiophen-2-yl)pyrimidin-2-ylamino]-phenyl}-ethanol (15 mg, 0.04 mmol), 2,6-dimethlphenylboronic acid (7.2 mg, 0.048 mmol) and PdCl2(dppf)2 (1.6 mg, 0.002 mmol) were combined in Smith microwave vial (0.2-5.0 mL) in degassed DMA (300 uL) and 2 M Na2CO3 (250 uL). The mixture was micro waved at 165° C. for 900 s. The mixture was diluted with 500 uL DMSO and purified directly by preparative HPLC to afford 1-(3-{4-[5-(2,6-dimethylphenyl)-thiophen-2-yl]-pyrimidin-2-ylamino}-phenylethanol (4.9 mg, 30% yield). 1H NMR (500 MHz, DMSO-d6) δ 1.29 (d, J=6.5 Hz, 3H), 2.14 (s, 6H), 4.64 (m, 1H), 5.07 (d, J=3.5 Hz, 1H), 6.91 (d, J=8 Hz, 1H), 7.02 (d, J=4 Hz, 1H), 7.16-7.25 (m, 4H), 7.35 (d, J=5 Hz, 1H), 7.60 (d, J=8 Hz, 1H), 7.84 (br t, 1H), 8.03 (d, J=3.5 Hz, 1H), 8.48 (d, J=5 Hz, 1H), 9.58 (s, 1H). MS: m/z 402 (M+H+).

Workup

  1. custompurified directly by preparative HPLC

Sources & evidence

ORD record
ord-24187921ad6a423b932fe35b2953a0c7
Source dataset
uspto-grants-2011_07
Patent number
US07977481B2

Reaction notes

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