Toluene → (Rac)-Pyrotinib

HRID 1397072ノート

反応式

HRID 1397072 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[CH2:66][CH2:65][CH2:64][CH:63]1[CH:67]=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:67]/[CH:63]4[CH2:64][CH2:65][CH2:66][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 150598951-Methylpyrrolidine-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 49847911(Rac)-Pyrotinib収率 20.8%

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 (3 g, 4.40 mmol) was dissolved in 30 mL of tetrahydrofuran in a dry ice bath, followed by dropwise addition of a solution of lithium bis(trimethylsilyl)amide (1 M) in toluene (9.6 mL, 8.80 mmol). After the mixture was stirred for 30 minutes, a solution of 1-methylpyrrolidine-2-carbaldehyde 10e (1 g, 8.80 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 24 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-methylpyrrolidin-2-yl)prop-2-enamide 10 (500 mg, yield 20.8%) as a yellow solid.

後処理

  1. stirringThe reaction mixture was stirred for another 30 minutes
  2. stirringstirred for 24 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-cc16f32c2e394c618f72bbe3e8efb169
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…