1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [4-(Furan-2-carbonyl)piperazin-1-yl](4-{4-[4-(morpholine-4-sulfonyl)-phenyl]pyrimidin-2-ylamino}phenyl)methanone

HRID 33462

Reaktionsgleichung

Reaktionsgleichung von HRID 33462
[N:1]1([S:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=4)[N:17]=3)=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[O:32]1[CH:36]=[CH:35][CH:34]=[C:33]1[C:37]([N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)=[O:38].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C1COCC1.C(Cl)Cl>[O:32]1[CH:36]=[CH:35][CH:34]=[C:33]1[C:37]([N:39]1[CH2:40][CH2:41][N:42]([C:27]([C:26]2[CH:25]=[CH:24][C:23]([NH:22][C:18]3[N:17]=[C:16]([C:13]4[CH:14]=[CH:15][C:10]([S:7]([N:1]5[CH2:2][CH2:3][O:4][CH2:5][CH2:6]5)(=[O:9])=[O:8])=[CH:11][CH:12]=4)[CH:21]=[CH:20][N:19]=3)=[CH:31][CH:30]=2)=[O:28])[CH2:43][CH2:44]1)=[O:38]

Komponenten

7

Edukt 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 5502061-(2-Furoyl)piperazineHCID 219059994-{4-[4-(Morpholine-4-sulfonyl)-phenyl]-pyrimidin-2-ylamino}benzoic Acid

Produkt 1

HCID 21906006[4-(Furan-2-carbonyl)piperazin-1-yl](4-{4-[4-(morpholine-4-sulfonyl)-phenyl]pyrimidin-2-ylamino}phenyl)methanoneAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

4-{4-[4-(Morpholine-4-sulfonyl)-phenyl]-pyrimidin-2-ylamino}-benzoic acid (0.25 g, 0.57 mmol) was dissolved in THF (5 mL). To this solution was added 1-furoylpiperazine (0.123 g), EDCI (0.131 g), and HOBt (0.092 g). The mixture was stirred 12 h. The mixture was then diluted with CH2Cl2 (20 mL) and washed with 2% NaOH (aq, 30 mL), water (30 mL), and then brine (30 mL). The organic layer was dried (Na2SO4), filtered, and concentrated. The crude solid was subjected to preparatory HPLC (20-70 acetonitrile/water gradient, 20 min). The desired fractions were concentrated to remove most of the acetonitrile, and then the aqueous mixture was extracted with CH2Cl2/2% NaOH (aq). The organic layer was dried (Na2SO4), filtered, and concentrated to afford [4-(furan-2-carbonyl)piperazin-1-yl](4-{4-[4-(morpholine-4-sulfonyl)-phenyl]pyrimidin-2-ylamino}phenyl)methanone (0.177 g, 52%): HPLC Retention Time; 9.62 min. (Method B) M+H=603.3

Aufarbeitung

  1. washwashed with 2% NaOH (aq, 30 mL), water (30 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customwas subjected to preparatory HPLC (20-70 acetonitrile/water gradient, 20 min)
  6. concentrationThe desired fractions were concentrated
  7. customto remove most of the acetonitrile
  8. extractionthe aqueous mixture was extracted with CH2Cl2/2% NaOH (aq)
  9. dry with materialThe organic layer was dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-400ca35375cc4d869f4f000af3c7e085
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07429599B2

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