Binap, (A+-)- → 5-Chloro-6-(4-[2-(3-chloro-4-fluoro-phenyl)-6-morpholin-4-yl-pyridin-4-yl]-piperazin-1-yl}-nicotinic acid ethyl ester

HRID 1444121Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[C:10]([Cl:15])[CH:9]=2)[N:5]=[C:4]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[CH:3]=1.[CH2:22]([O:24][C:25](=[O:39])[C:26]1[CH:31]=[C:30]([Cl:32])[C:29]([N:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)=[N:28][CH:27]=1)[CH3:23].CC([O-])(C)C.[K+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:22]([O:24][C:25](=[O:39])[C:26]1[CH:31]=[C:30]([Cl:32])[C:29]([N:33]2[CH2:38][CH2:37][N:36]([C:2]3[CH:3]=[C:4]([N:16]4[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[N:5]=[C:6]([C:8]4[CH:13]=[CH:12][C:11]([F:14])=[C:10]([Cl:15])[CH:9]=4)[CH:7]=3)[CH2:35][CH2:34]2)=[N:28][CH:27]=1)[CH3:23]

Participants

Conditions

Temperature: 80 °C

Procedure

To a de-gassed mixture of 4-{4-bromo-6-(3-chloro-4-fluoro-phenyl)-pyridin-2yl}-morpholine (50 mg, 0.135 mmol), 5-chloro-6-piperazin-1-yl-nicotinic acid ethyl ester (0.162 mmol), and 1M (THF) t-BuOK (0.162 mmol), in toluene (3 mL) under nitrogen add Pd2(dba)3 (0.0054 mmol) and BINAP (0.0067 mmol). Stir the mixture at 80° C. for 16 h, concentrate, extract with EtOAc. Dry over Na2SO4, concentrate under vacuum, and purify by preparative TLC (3:1 hexanes/EtOAc) to give the title compound.

Workup

concentrationconcentrate
extractionextract with EtOAc
dry with materialDry over Na2SO4
concentrationconcentrate under vacuum
custompurify by preparative TLC (3:1 hexanes/EtOAc)

Sources & evidence

ORD record: ord-05f80cbc5bae4220a0dfb878d00e6c1a
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07662830B2

Reaction notes

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