Isopropanol → HCID 44816299, Verbindung

HRID 1697889Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1697889
[CH2:1]([NH:3][C:4](=[O:34])[NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:15]3[CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][C:16]=3[N:17]=2)=[CH:8][CH:7]=1)[CH3:2].C(O)(C(F)(F)F)=O.C(O)(C)C.C(=O)([O-])[O-]>ClCCl.C1(C)C=CC=CC=1>[CH2:1]([NH:3][C:4]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[C:15]3[CH2:20][NH:19][CH2:18][C:16]=3[N:17]=2)=[CH:8][CH:7]=1)=[O:34])[CH3:2]

Komponenten

7

Edukt 4

HCID 3776IsopropanolHCID 6422Trifluoroacetic acidHCID 19660Carbonate IonHCID 46912801HCID 46912801, Verbindung

Produkt 1

HCID 44816299HCID 44816299, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Step 3—Synthesis of d: tert-butyl 2-(4-(3-ethylureido)phenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (c, 1.74 mmol) was dissolved in dichloromethane (5 mL), then TFA (3 mL) was added. The mixture was stirred at room temperature for 2 hours. Isopropanol and toluene were added and the resulting mixture was concentrated in vacuo. The resulting residue was azeotroped with toluene two more times. Methanol and methylene chloride (4 mL each) were added to the resulting residue, then PS-carbonate (2.5-3.5 mmol N/gram resin, 1.45 g) was added. The mixture was stirred at room temperature until the pH reached >7 (˜1 hr). The mixture was filtered, the resin was washed with methanol and dichloromethane. The filtrate was concentrated to provide 1-ethyl-3-(4-(4-morpholino-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea as a free amine, which was used in the next step. An aliquot was purified by reverse-phase HPLC to give the pure desired product: 1H NMR (400 MHz, DMSO) δ 9.57 (s, 1H), 8.75 (s, 1H), 8.19 (d, J=8.9, 2H), 7.50 (d, J=8.9, 2H), 6.38-6.08 (m, 1H), 4.71 (s, 2H), 4.38 (s, 2H), 3.72 (s, 8H), 3.24-3.03 (m, 2H), 1.06 (t, J=7.2, 3H); LC-MS: m/z=+369 (M+H)+.

Aufarbeitung

  1. concentrationthe resulting mixture was concentrated in vacuo
  2. customThe resulting residue was azeotroped with toluene two more times
  3. additionMethanol and methylene chloride (4 mL each) were added to the resulting residue
  4. stirringThe mixture was stirred at room temperature until the pH
  5. custom>7 (˜1 hr)
  6. filtrationThe mixture was filtered
  7. washthe resin was washed with methanol and dichloromethane
  8. concentrationThe filtrate was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-3de7189012594c4cb5434f09ca7d12fe
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08163763B2

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