N-methyl-2-pyrrolidone → 5-{9-Isobutyl-8-[4-(methylsulfonyl)-1,4-diazepan-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine

HRID 421355

Reaktionsgleichung

Reaktionsgleichung von HRID 421355
[NH:1]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.CN1CCCC1=O.Cl[C:16]1[N:17]([CH2:38][CH:39]([CH3:41])[CH3:40])[C:18]2[C:23]([N:24]=1)=[C:22]([N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)[N:21]=[C:20]([C:31]1[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=1)[N:19]=2.[S:42](Cl)([CH3:45])(=[O:44])=[O:43]>C(N(CC)CC)C>[CH2:38]([N:17]1[C:16]([N:1]2[CH2:7][CH2:6][CH2:5][N:4]([S:42]([CH3:45])(=[O:44])=[O:43])[CH2:3][CH2:2]2)=[N:24][C:23]2[C:18]1=[N:19][C:20]([C:31]1[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=1)=[N:21][C:22]=2[N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)[CH:39]([CH3:41])[CH3:40]

Komponenten

6

Edukt 4

HCID 13387N-methyl-2-pyrrolidoneHCID 31297Methanesulfonyl chlorideHCID 68163Hexahydro-1,4-diazepineHCID 593335495-(8-Chloro-9-isobutyl-6-morpholino-9H-purin-2-yl)pyrimidin-2-amine

Produkt 1

HCID 593336605-{9-Isobutyl-8-[4-(methylsulfonyl)-1,4-diazepan-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amineAusbeute 110,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

Homopiperazine (130 mg, 1.3 mmol) and N-methylpyrrolidone (1 ml) were added to 5-(8-chloro-9-isobutyl-6-morpholin-4-yl-9H-purin-2-yl)pyrimidin-2-amine (100 mg, 0.26 mmol) and the resulting mixture stirred at 120° C. for 2 hours. The reaction mixture was cooled and partitioned with methylene chloride and water, the organic layer was dried over magnesium sulfate, and the solvent was concentrated under reduced pressure. Triethylamine (110 μl) and mesyl chloride (45 μl, 0.58 mmol) were added to the resulting mixture and the resulting mixture was stirred for 0.5 hours. The reaction mixture was partitioned with ethyl acetate and water and the organic layer was dried over magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by preparative HPLC (column, NOMURA Develosil Combi-RP-5; mobile phase, acetonitrile/water/formic acid) to give the title compound (153 mg, 75%) as a white solid.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned with methylene chloride and water
  3. dry with materialthe organic layer was dried over magnesium sulfate
  4. concentrationthe solvent was concentrated under reduced pressure
  5. stirringthe resulting mixture was stirred for 0.5 hours
  6. customThe reaction mixture was partitioned with ethyl acetate and water
  7. dry with materialthe organic layer was dried over magnesium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was purified by preparative HPLC (column, NOMURA Develosil Combi-RP-5; mobile phase, acetonitrile/water/formic acid)

Quellen und Nachweise

ORD-Eintrag
ord-42295b25c6bb4432a476fc87dcd0cd31
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08097622B2

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