1,2-Dibromo-3-methylbenzene → N-(3-bromo-5-methylphenyl)-N'-(7-chloroquinolin-4-yl)cyclohexane-1,4-diamine

HRID 2415627Notes

Reaction equation

HRID 2415627 reaction equation
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.CC(C)([O-])C.[Na+].[Cl:53][C:54]1[CH:63]=[C:62]2[C:57]([C:58]([NH:64][C@H:65]3[CH2:70][CH2:69][C@@H:68]([NH:71]C4C5C(=CC(Cl)=CC=5)N=CC=4)[CH2:67][CH2:66]3)=[CH:59][CH:60]=[N:61]2)=[CH:56][CH:55]=1.[Br:83][C:84]1[C:85](Br)=[C:86]([CH3:90])[CH:87]=[CH:88][CH:89]=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]>[Br:83][C:84]1[CH:89]=[C:88]([NH:71][CH:68]2[CH2:67][CH2:66][CH:65]([NH:64][C:58]3[C:57]4[C:62](=[CH:63][C:54]([Cl:53])=[CH:55][CH:56]=4)[N:61]=[CH:60][CH:59]=3)[CH2:70][CH2:69]2)[CH:87]=[C:86]([CH3:90])[CH:85]=1

Participants

7

Reactant 4

HCID 346801,2-Dibromo-3-methylbenzeneHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 178477879HCID 178477879, compound

Product 1

HCID 10216894N-(3-bromo-5-methylphenyl)-N'-(7-chloroquinolin-4-yl)cyclohexane-1,4-diamineYield 16%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A dry 250 mL 3-necked flask was charged with Pd2(dba)3 (266 mg, 2 mol %), BINAP, 384 mg, 4 mol %), and sodium t-butoxide (2.2 g, 0.023 mol) in 50 mL dry toluene. After 5 minutes, 23A cis-N,N′-bis(7-chloroquinolin-4-yl)cyclohexane-1,4-diamine (4.00 g, 0.0145 mol) was added in one portion followed by dibromotoluene (3.6 g, 0.0145 mol). The solution was heated at 70° C. under nitrogen overnight. The contents were filtered, concentrated and the residue was purified by flash chromatography (5% methanol in dichloromethane) to provide 1.03 g, a 16% yield. MS (ESI(+)Q1MS m/z 445 (M+2 H)+; 1 H NMR (300 MHz, MeOH) δ ppm 8.51 (d, 1 H), 8.37 (d, 1 H), 7.86 (d, 1 H), 7.69 (dd, 1 H), 6.96 (d, 1 H), 6.66 (s, 1 H), 6.61 (s, 1 H), 6.49 (s, 1 H), 3.98 (m, 1 H), 3.63 (m, 1 H), 2.22 (s, 3 H), 1.85-2.01 (m, 8 H).

Workup

  1. filtrationThe contents were filtered
  2. concentrationconcentrated
  3. customthe residue was purified by flash chromatography (5% methanol in dichloromethane)
  4. customto provide 1.03 g

Sources & evidence

ORD record
ord-8df2fb228ecb4c3ea8fd2e40f61713fd
Source dataset
uspto-grants-2004_11
Patent number
US06818772B2

Reaction notes

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