2,8-Dichloro-quinoline-3-carbaldehyde → (8-Chloro-2-(pyridin-2-yl)quinolin-3-yl)methanamine

HRID 2044852Notes

Reaction equation

HRID 2044852 reaction equation
BrC1C=CC=[C:6]2[C:11]=1[N:10]=[C:9](C1C=CC=C(F)C=1)[C:8](CN1C(=O)C3C(=CC=CC=3)C1=O)=[CH:7]2.ClC1C(C=O)=CC2C(=C(Cl)C=CC=2)N=1.[Cl:45][C:46]1[C:55]([CH2:56][N:57]2[C:65](=[O:66])[C:64]3[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=3)[C:58]2=[O:67])=[CH:54][C:53]2[C:48](=[C:49]([Cl:68])[CH:50]=[CH:51][CH:52]=2)[N:47]=1.[Br-].N1C=CC=CC=1[Zn+]>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:45][C:46]1[C:55]([CH2:56][N:57]2[C:65](=[O:66])[C:64]3[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=3)[C:58]2=[O:67])=[CH:54][C:53]2[C:48](=[C:49]([Cl:68])[CH:50]=[CH:51][CH:52]=2)[N:47]=1.[Cl:68][C:49]1[CH:50]=[CH:51][CH:52]=[C:53]2[C:48]=1[N:47]=[C:46]([C:9]1[CH:8]=[CH:7][CH:6]=[CH:11][N:10]=1)[C:55]([CH2:56][NH2:57])=[CH:54]2

Participants

8

Reactant 4

HCID 149171252,8-Dichloro-quinoline-3-carbaldehydeHCID 577078392-((8-Bromo-2-(3-fluorophenyl)quinolin-3-yl)methyl)isoindoline-1,3-dioneHCID 577080182-((2,8-Dichloroquinolin-3-yl)methyl)isoindoline-1,3-dioneHCID 178418723HCID 178418723, compound

Product 2

HCID 57707932(8-Chloro-2-(pyridin-2-yl)quinolin-3-yl)methanamineHCID 577080182-((2,8-Dichloroquinolin-3-yl)methyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

2-((2,8-Dichloroquinolin-3-yl)methyl)isoindoline-1,3-dione was prepared in the similar manner as 2-((8-bromo-2-(3-fluorophenyl)quinolin-3-yl)methyl)-isoindoline-1,3-dione from 2,8-dichloroquinoline-3-carbaldehyde. A mixture of 2-((2,8-dichloroquinolin-3-yl)methyl)isoindoline-1,3-dione (71 mg, 0.2 mmol), 2-pyridylzinc bromide (0.5 M, 0.8 mL, 2.0 eq) and tetrakis(triphenylphosphine) palladium (11 mg, 5%) in dioxane (3 mL) was purged with N2 and heated to 65° C. After 12 h, the reaction was cooled to rt and quenched with NH4Cl solution. After work up, The residue containing a mixture of 2-(((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)isoindoline-1,3-dione and 2-(((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)carbamoyl)benzoic acid was treated with NH2NH2 (31 μL) in EtOH (1 mL) at reflux. After usual work up, the residue was purified on column chromatography on silica gel (DCM/MeOH/Et3N, 20/1/0.1) to give a pale yellow solid as (8-chloro-2-(pyridin-2-yl)quinolin-3-yl)methanamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.60 (d, J=8.0 Hz, 1H), 8.31 (d, J=8.0 Hz, 1H), 8.17 (s, 1H), 7.84 (t, J=8.0 Hz, 1H), 7.74 (d, J=8.0 Hz, 1H), 7.66 (d, J=8.0 Hz, 1H), 7.38 (t, J=8.0 Hz, 1H), 7.30 (t, J=8.0 Hz, 1H), 4.13 (s, 3H). Mass Spectrum (ESI) m/e=270 (M+1).

Workup

  1. customwas purged with N2
  2. temperaturethe reaction was cooled to rt
  3. customquenched with NH4Cl solution
  4. additionAfter work up, The residue containing
  5. additiona mixture of 2-(((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)isoindoline-1,3-dione and 2-(((8-chloro-2-(pyridin-2-yl)-quinolin-3-yl)methyl)carbamoyl)benzoic acid
  6. additionwas treated with NH2NH2 (31 μL) in EtOH (1 mL)
  7. temperatureat reflux
  8. customAfter usual work up, the residue was purified on column chromatography on silica gel (DCM/MeOH/Et3N, 20/1/0.1)

Sources & evidence

ORD record
ord-d14f9acfee1d4ac893fbccb8391613a4
Source dataset
uspto-grants-2013_11
Patent number
US08586739B2

Reaction notes

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