Cesium carbonate → Methyl 3-(8-(6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate

HRID 1755347노트

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HRID 1755347 반응식
Br[C:2]1[C:3]2[N:4]([CH:18]=[CH:19][N:20]=2)[N:5]=[C:6]([C:8]2[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=2)[C:11]([O:13][CH3:14])=[O:12])[CH:7]=1.[CH3:21][O:22][CH2:23][CH:24]1[CH2:28][CH2:27][CH2:26][N:25]1[C:29]1[N:34]=[C:33]([NH2:35])[CH:32]=[CH:31][CH:30]=1.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.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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]>[CH3:21][O:22][CH2:23][CH:24]1[CH2:28][CH2:27][CH2:26][N:25]1[C:29]1[N:34]=[C:33]([NH:35][C:2]2[C:3]3[N:4]([CH:18]=[CH:19][N:20]=3)[N:5]=[C:6]([C:8]3[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=3)[C:11]([O:13][CH3:14])=[O:12])[CH:7]=2)[CH:32]=[CH:31][CH:30]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 86682703HCID 86682703, 화합물HCID 866827206-(2-(Methoxymethyl)pyrrolidin-1-yl)pyridin-2-amine

생성물 1

HCID 86682721Methyl 3-(8-(6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate수율 36.3%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

A mixture of methyl 3-(8-bromoimidazo[1,2-b]pyridazin-6-yl)benzoate (0.10 g, 0.3 mmol), 6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-amine (0.083 g, 0.4 mmol), Pd2(dba)3 (0.019 g, 0.033 mmol), BINAP (0.083 g, 0.134 mmol) and Cs2CO3 (0.326 g, 1.0 mmol) in dioxane (20 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15) to afford methyl 3-(8-(6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (0.050 g) as a yellow solid. LC-MS: [M+1]+=459, tR=1.985 min. This contained some unidentified impurities and was used directly without further purification.

후처리

  1. concentrationthen concentrated in vacuo
  2. customThe residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15)

출처 및 근거

ORD 기록
ord-0985f44236c940068ecdfce53bba94e7
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09169259B2

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