Toluene → Pyrotinib

HRID 2199346Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2199346
[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][C@@H: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]/[C@H: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

Komponenten

6

Edukt 4

HCID 1140TolueneHCID 2733832Lithium HexamethyldisilazideHCID 53829762(2R)-1-methylpyrrolidine-2-carbaldehydeHCID 86667261Diethyl (2-((4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)amino)-2-oxoethyl)phosphonate

Produkt 1

HCID 51039030PyrotinibAusbeute 19,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

N-[4-[[3-Chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-2-diethoxyphosphoryl-acetamide 1d (250 mg, 0.40 mmol) was dissolved in 10 mL of dry tetrahydrofuran in a dry ice bath, followed by dropwise addition of a solution of lithium bis(trimethylsilyl)amide (1 M) in toluene (440 μL, 0.44 mmol). The reaction mixture was stirred for 30 minutes, added dropwise with a solution of (2R)-1-methylpyrrolidine-2-carbaldehyde 5c (90 mg, 0.80 mmol) in 5 mL of tetrahydrofuran, and stirred for 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-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide 5 (46 mg, yield 19.7%) as a yellow solid.

Aufarbeitung

  1. stirringstirred for 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

Quellen und Nachweise

ORD-Eintrag
ord-77eabda6bd484b3da3fab19ada9f34e2
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09358227B2

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