Toluene → (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-(1-methyl-2-piperidyl)prop-2-enamide

HRID 1397064ノート

反応式

HRID 1397064 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:39][CH2:40][CH3:41])=[C:24]([NH:27][C:28](=[O:38])[CH2:29]P(OCC)(OCC)=O)[CH:25]=3)[N:20]=[CH:19][C:18]=2[C:42]#[N:43])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1(C)C=CC=CC=1.[CH3:61][N:62]1[CH2:67][CH2:66][CH2:65][CH2:64][CH:63]1[CH:68]=O>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:39][CH2:40][CH3:41])=[C:24]([NH:27][C:28](=[O:38])/[CH:29]=[CH:68]/[CH:63]4[CH2:64][CH2:65][CH2:66][CH2:67][N:62]4[CH3:61])[CH:25]=3)[N:20]=[CH:19][C:18]=2[C:42]#[N:43])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

参加物

6

反応物 4

HCID 1140TolueneHCID 2733832Lithium HexamethyldisilazideHCID 138378701-Methylpiperidine-2-carbaldehydeHCID 86667261Diethyl (2-((4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)amino)-2-oxoethyl)phosphonate

生成物 1

HCID 51038276(E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-(1-methyl-2-piperidyl)prop-2-enamide収率 4.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

N-[4-[[3-Chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-2-diethoxyphosphoryl-acetamide 1d (300 mg, 0.48 mmol) was dissolved in 10 mL of tetrahydrofuran in a dry ice bath, followed by dropwise addition of a solution of lithium bis(trimethylsilyl)amide (1 M) in toluene (530 μL, 0.53 mmol). After stirring for 30 minutes, a solution of 1-methylpiperidine-2-carbaldehyde 6b (120 mg, 0.96 mmol) in 5 mL of tetrahydrofuran was added dropwise. The reaction mixture was stirred for another 30 minutes, then warmed up to room temperature and stirred for 12 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography with elution system A to obtain the title compound (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-(1-methyl-2-piperidyl)prop-2-enamide 6 (14 mg, yield 4.9%) as a yellow solid.

後処理

  1. stirringThe reaction mixture was stirred for another 30 minutes
  2. stirringstirred for 12 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customthe resulting residue was purified by silica gel column chromatography with elution system

出典と根拠

ORDレコード
ord-e678f49c41b849148bc8a3f0b1bbe02c
出典データセット
uspto-grants-2014_12
特許番号
US08901140B2

反応ノート

読み込み中…