Dimethylformamide → Diethyl [4-({4-[(7-cyano-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate

HRID 1947953Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1947953
[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:32]=[CH:31][C:30](Br)=[C:29]4[C:25]=3[C:26](=[O:35])[N:27]([CH3:34])[CH2:28]4)[C:20]([C:36]([F:39])([F:38])[F:37])=[CH:19][N:18]=2)=[CH:12][CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[CH3:40][N:41](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:32]=[CH:31][C:30]([C:40]#[N:41])=[C:29]4[C:25]=3[C:26](=[O:35])[N:27]([CH3:34])[CH2:28]4)[C:20]([C:36]([F:39])([F:38])[F:37])=[CH:19][N:18]=2)=[CH:12][CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]

Komponenten

5

Edukt 2

HCID 6228DimethylformamideHCID 58292897Diethyl [4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate

Produkt 1

HCID 58292876Diethyl [4-({4-[(7-cyano-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysator

Versuchsvorschrift

A mixture of diethyl[4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate (20.0 mg, 0.0318 mmol), zinc cyanide (3.74 mg, 0.0318 mmol), Pd(PPh3)4 (5.52 mg, 0.00477 mmol) in DMF (0.5 mL) was evacuated and purged with N2 three times. The mixture was irradiated in a microwave reactor at 150° C. for 5 minutes. The crude mixture was passed though a Thiol-SPE cartridge to remove Pd and subsequently purified by MDP. The title compound was obtained as white solid (13.5 mg, 74% yield). 1H NMR (400 MHz, CDCl3) δ=1.29 (t, J=7.1 Hz, 6H), 3.20 (d, J=21.5 Hz, 2H), 3.24 (s, 3H), 4.09 (quin, J=7.3 Hz, 4H), 4.54 (s, 2H), 7.31-7.39 (m, 2H), 7.49 (d, J=8.1 Hz, 2H), 7.56 (br. s., 1H), 7.70 (d, J=8.8 Hz, 1H), 8.44 (s, 1H), 8.70 (d, J=8.3 Hz, 1H), 10.85 (s, 1H). MS (ES+): m/z 575.21 (100) [MH+] HPLC: tR=1.08 min (UPLC, purity).

Aufarbeitung

  1. customwas evacuated
  2. custompurged with N2 three times
  3. customThe mixture was irradiated in a microwave reactor at 150° C. for 5 minutes
  4. customto remove Pd
  5. customsubsequently purified by MDP

Quellen und Nachweise

ORD-Eintrag
ord-f94d4bcd46444c8c9d2d5e6cb1025b80
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399433B2

Notizen zur Reaktion

Wird geladen…