Toluene → (E)-3-[(2S,4R)-4-(tert-butyl(dimethyl)silyl)oxy-1-methyl-pyrrolidin-2-yl]-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]prop-2-enamide

HRID 1397056ノート

反応式

HRID 1397056 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.[Si:61]([O:68][C@H:69]1[CH2:73][N:72]([CH3:74])[C@H:71]([CH:75]=O)[CH2:70]1)([C:64]([CH3:67])([CH3:66])[CH3:65])([CH3:63])[CH3:62]>O1CCCC1>[Si:61]([O:68][C@H:69]1[CH2:73][N:72]([CH3:74])[C@H:71](/[CH:75]=[CH:29]/[C:28]([NH:27][C:24]2[CH:25]=[C:26]3[C:21](=[CH:22][C:23]=2[O:39][CH2:40][CH3:41])[N:20]=[CH:19][C:18]([C:42]#[N:43])=[C:17]3[NH:16][C:4]2[CH:5]=[CH:6][C:7]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=3)=[C:2]([Cl:1])[CH:3]=2)=[O:38])[CH2:70]1)([C:64]([CH3:67])([CH3:66])[CH3:65])([CH3:62])[CH3:63]

参加物

6

反応物 4

HCID 1140TolueneHCID 2733832Lithium HexamethyldisilazideHCID 86667261Diethyl (2-((4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)amino)-2-oxoethyl)phosphonateHCID 86667262(2S,4R)-4-(tert-butyl(dimethyl)silyl)oxy-1-methyl-pyrrolidine-2-carbaldehyde

生成物 1

HCID 67979671(E)-3-[(2S,4R)-4-(tert-butyl(dimethyl)silyl)oxy-1-methyl-pyrrolidin-2-yl]-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]prop-2-enamide収率 61.2%

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 (418 mg, 0.67 mmol) was dissolved in 2.5 mL of tetrahydrofuran in a dry ice bath, followed by dropwise addition of a solution of lithium bis(trimethylsilyl)amide (1 M) in toluene (1 mL, 1 mmol). After the mixture was stirred for 45 minutes, a solution of (2S,4R)-4-(tert-butyl(dimethyl)silyl)oxy-1-methyl-pyrrolidine-2-carbaldehyde 3e (326 mg, 1.34 mmol) in 2.5 mL of tetrahydrofuran was added, and stirred for another 1 hour, 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)-3-[(2S,4R)-4-(tert-butyl(dimethyl)silyl)oxy-1-methyl-pyrrolidin-2-yl]-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]prop-2-enamide 3f (292 mg, yield 61.2%) as a yellow solid.

後処理

  1. stirringstirred for another 1 hour
  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-0b4614f881b344a8b69a8a44e00837b4
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…