Cesium carbonate → (6-Methoxy-isoquinolin-3-yl)-(4-pyrrolidin-1-ylmethyl-pyridin-2-yl)-amine

HRID 1257120

반응식

HRID 1257120 반응식
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:43][O:44][C:45]1[CH:46]=[C:47]2[C:52](=[CH:53][CH:54]=1)[CH:51]=[N:50][C:49]([NH2:55])=[CH:48]2.Cl[C:57]1[CH:62]=[C:61]([CH2:63][N:64]2[CH2:68][CH2:67][CH2:66][CH2:65]2)[CH:60]=[CH:59][N:58]=1.C([O-])([O-])=O.[Cs+].[Cs+]>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].C1COCC1>[CH3:43][O:44][C:45]1[CH:46]=[C:47]2[C:52](=[CH:53][CH:54]=1)[CH:51]=[N:50][C:49]([NH:55][C:59]1[CH:60]=[C:61]([CH2:63][N:64]3[CH2:65][CH2:66][CH2:67][CH2:68]3)[CH:62]=[CH:57][N:58]=1)=[CH:48]2

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 233211576-Methoxyisoquinolin-3-amineHCID 581138712-Chloro-4-(pyrrolidin-1-ylmethyl)pyridine

생성물 1

HCID 44612348(6-Methoxy-isoquinolin-3-yl)-(4-pyrrolidin-1-ylmethyl-pyridin-2-yl)-amine수율 40%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매

실험 절차

Pd2(dba)3(102 mmg, 0.11 mmol) and xantphos (92 mg, 0.16 mmol) were added to a solution of 6-methoxyisoquinolin-3-amine (195 mg, 1.12 mmol) (Preparation C-10), 2-chloro-4-pyrrolidin-1-ylmethyl-pyridine (220 mg, 1.12 mmol) (Preparation B-11) and Cs2CO3 (500 mg, 1.53 mmol) in toluene (50 mL). The suspension was heated under reflux overnight, and THF (50 mL) was added in to dilute the mixture. After filtration, the filtrate was concentrated. The crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/1) and afforded the title compound (150 mg, 40% yield) as a yellow solid. 1H NMR (300 MHz, DMSO-d6): 8.84 (s, 1H), 8.27˜8.29 (m, 2H), 7.73 (d, J=8.7 Hz, 1 H), 7.60 (bs, 1H), 6.99˜7.08 (m, 3H), 7.02 (s, 1H), 6.86 (d, J=5.1 Hz, 1H), 3.94 (s, 3H), 3.62 (s, 2H), 2.58 (m, 4H), 1.83 (m, 4H); MS: m/z 335.2 (M+H+).

후처리

  1. temperatureThe suspension was heated
  2. temperatureunder reflux overnight
  3. additionto dilute the mixture
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated
  6. customThe crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/1)

출처 및 근거

ORD 기록
ord-3ab79e0739224c7591c18a39dc1a4aae
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461339B2

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