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

HRID 2044852노트

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HRID 2044852 반응식
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

참가 물질

8

반응물 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, 화합물

생성물 2

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

시약·촉매·용매 2

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 312751,4-Dioxane용매

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온도
65 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-d14f9acfee1d4ac893fbccb8391613a4
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08586739B2

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