Potassium Carbonate → [2-(4-{4-[4-Methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenylcarbamoyl]-benzyl}-piperazin-1-yl)-ethyl]-phosphonic acid diethyl ester

HRID 2220141

Reaktionsgleichung

Reaktionsgleichung von HRID 2220141
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:23])[C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:12][CH:11]=2)=[CH:4][C:3]=1[NH:24][C:25]1[N:30]=[C:29]([C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)[CH:28]=[CH:27][N:26]=1.Br[CH2:38][CH2:39][P:40](=[O:47])([O:44][CH2:45][CH3:46])[O:41][CH2:42][CH3:43].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:42]([O:41][P:40]([CH2:39][CH2:38][N:20]1[CH2:19][CH2:18][N:17]([CH2:16][C:13]2[CH:12]=[CH:11][C:10]([C:9](=[O:23])[NH:8][C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([NH:24][C:25]4[N:30]=[C:29]([C:31]5[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=5)[CH:28]=[CH:27][N:26]=4)[CH:4]=3)=[CH:15][CH:14]=2)[CH2:22][CH2:21]1)(=[O:47])[O:44][CH2:45][CH3:46])[CH3:43]

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 79218Diethyl (2-bromoethyl)phosphonateHCID 9869737Cgp-74588

Produkt 1

HCID 59772964[2-(4-{4-[4-Methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenylcarbamoyl]-benzyl}-piperazin-1-yl)-ethyl]-phosphonic acid diethyl esterAusbeute 72,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A mixture of N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-piperazin-1-ylmethyl-benzamide (30 mg, 0.06 mmol, Zimmermann et al., Bioorg. Med. Chem. Lett. 1996, 6, 1221), diethyl 2-bromoethylphosphonate (30 μL, 0.12 mmol) and K2CO3 (20 mg, 0.16 mmol) in 2.5 mL of DMF was heated at 110° C. for 8 hours when most of the starting materials were consumed as judged by LCMS analysis. The solid material was filtered off. The filtrate was diluted with water and then extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated to dryness. The crude material was purified by silica gel chromatography using 10% MeOH/CH2Cl2 to provide 28 mg (55%) of the desired product. 1H NMR (300 MHz, CDCl3) δ 1.32 (t, 6H), 1.92-20.3 (m, 4H), 2.35 (s, 3H), 2.5 (bs, 6H), 2.64 (m, 2H), 3.56 (s, 2H), 4.05-4.14 (m, 4H), 7.07(s, 1H), 7.18 (d, 2H, J=5 Hz), 7.30 (dd, 1H, J=6, 8 Hz), 7.33-7.45 (m, 3H), 7.84 (d, 2H, J=8 Hz), 8.01 (s, 1H), 8.51 (dd, 2H, J=4, 9 Hz), 8.58 (d, 1H, J=2 Hz), 8.70 (dd, 1H, J=2, 5 Hz), 9.25 (s, 1H); 31P (121.4 MHz, CDCl3) δ 30.5; MS (m/z) 644 [M+H]+.

Aufarbeitung

  1. customwere consumed
  2. filtrationThe solid material was filtered off
  3. additionThe filtrate was diluted with water
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. customThe crude material was purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-5196580ba9e34eedbf953266b82dbf80
Quelldatensatz
uspto-grants-2008_08
Patentnummer
US07417055B2

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