Dichloromethane → (Z)-3-chloro-N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(4-ethylpiperazin-1-yl)phenyl)acrylamide

HRID 58215Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 58215
[NH2:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH3:15])[CH2:10][CH2:9]2)[CH:5]=[CH:4][C:3]=1[NH:16][C:17]1[N:22]=[CH:21][N:20]=[C:19]([N:23]([CH3:39])[C:24]([NH:26][C:27]2[C:32]([Cl:33])=[C:31]([O:34][CH3:35])[CH:30]=[C:29]([O:36][CH3:37])[C:28]=2[Cl:38])=[O:25])[CH:18]=1.C(N(CC)CC)C.[Cl:47]/[CH:48]=[CH:49]\[C:50](O)=[O:51].C(Cl)Cl.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC>>[Cl:47]/[CH:48]=[CH:49]\[C:50]([NH:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:9][CH2:10][N:11]([CH2:14][CH3:15])[CH2:12][CH2:13]2)[CH:5]=[CH:4][C:3]=1[NH:16][C:17]1[CH:18]=[C:19]([N:23]([CH3:39])[C:24]([NH:26][C:27]2[C:32]([Cl:33])=[C:31]([O:34][CH3:35])[CH:30]=[C:29]([O:36][CH3:37])[C:28]=2[Cl:38])=[O:25])[N:20]=[CH:21][N:22]=1)=[O:51]

Komponenten

6

Edukt 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 643794cis-3-Chloroacrylic acidHCID 1180245461-(6-((2-Amino-4-(4-ethylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylurea

Produkt 1

HCID 118026047(Z)-3-chloro-N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(4-ethylpiperazin-1-yl)phenyl)acrylamideAusbeute 59,4 %

Versuchsvorschrift

The title compound was synthesized following the approach outlined in Procedure 2C (Example 108), modifying step (g) to the following procedure: To a solution of 1-(6-((2-amino-4-(4-ethylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylurea (11 g, 0.019 mmol), triethylamine (9.67 g, 0.096 mmol), and (Z)-3-chloroacrylic acid (2.43 g, 0.023 mmol) in DCM (0.4 ml, 6.21 mmol) was added a solution of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (21.9 g, 0.034 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 30 min. The mixture was concentrated and the residue was purified by silica gel column to obtain the title compound (7.5 mg, yield: 59%). 1H NMR (400 MHz, CDCl3) δ 1.29 (t, J=8.0 Hz, 3H) 2.90 (br. s., 4H) 3.27 (s, 3H) 3.45 (t, J=4.64 Hz, 4H) 3.91 (s, 6H) 5.90 (s, 1H) 6.32 (d, J=8.41 Hz, 1H) 6.52 (s, 1H) 6.59 (d, J=8.41 Hz, 1H) 6.73 (dd, J=8.78, 2.76 Hz, 1H) 7.09 (br. s., 1H) 7.24 (s, 2H) 7.83 (br. s., 1H) 8.36 (s, 1H) 8.69 (br. s., 1H) 12.52 (s, 1H); MS (ESI): 663.1 [M+H]+.

Aufarbeitung

  1. customThe title compound was synthesized
  2. concentrationThe mixture was concentrated
  3. customthe residue was purified by silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-f975372f7f1b4b91bac1d2a90c0dade9
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434697B2

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