Acetic Acid → HCID 178508612, Verbindung

HRID 51604

Reaktionsgleichung

Reaktionsgleichung von HRID 51604
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[CH:9][N:8]([CH:24]3[CH2:29][CH2:28][C:27](=O)[CH2:26][CH2:25]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[NH2:31][C@@H:32]1[CH2:36][CH2:35][NH:34][CH2:33]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl.O>[O:17]([C:14]1[CH:13]=[CH:12][C:11]([C:10]2[C:3]3[C:2]([NH2:1])=[N:7][CH:6]=[N:5][C:4]=3[N:8]([C@H:24]3[CH2:25][CH2:26][C@@H:27]([NH:31][C@@H:32]4[CH2:36][CH2:35][NH:34][CH2:33]4)[CH2:28][CH2:29]3)[CH:9]=2)=[CH:16][CH:15]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Komponenten

8

Edukt 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 1519352(3R)-pyrrolidin-3-amineHCID 5049666Sodium triacetoxyborohydrideHCID 22736171Protein kinase inhibitor 9

Produkt 1

HCID 178508612HCID 178508612, VerbindungAusbeute 24,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

A mixture of 4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexanone (1.00 g, 2.51 mmol), (3R)-(+)-3-aminopyrrolidine (0.65 g, 7.5 mmol), and acetic acid (0.43 mL, 7.5 mmol) in 1,2-dichloroethane (50 mL) was stirred at ambient temperature under an atmosphere of nitrogen for 45 minutes. Sodium triacetoxyborohydride (0.691 g, 3.26 mmol) was added and the mixture stirred at ambient temperature for 15 hours. Water (50 mL) and sodium bicarbonate (1.35 g, 16.1 mmol) were added and the mixture was stirred for 45 minutes. The reaction mixture was transferred to a separatory funnel and the organic layer was separated. The organic portion was dried over magnesium sulfate, filtered, and the solvent removed under reduced pressure to yield an oily brown solid. The compound was purified by flash chromatography on silica gel (1 L 10% MeOH in CH2Cl2, then 1 L 20% MeOH in CH2Cl2, followed by 500 mL 30% MeOH in CH2Cl2) to yield cis-5-(4-phenoxyphenyl)-7-{4-[(3R)tetrahydro-1H-3-pyrrolylamino]cyclohexyl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a beige solid (0.285 g, 0.608 mmol): 1H NMR (d6 DMSO, 400 MHz): δ H 8.13(1H, s), 7.39-7.49(5H, m), 7.07-7.17(5H, m), 6.09(2H, bs), 4.65 (1H, m), 3.29-3.35 (3H, m), 2.63-2.67(2H, m), 1.94-2.51(8H, m), 1.46-1.80(4H, m); RP-HPLC (Delta Pak C18, 5,μm, 300 A, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 12.59 min.

Aufarbeitung

  1. stirringthe mixture stirred at ambient temperature for 15 hours
  2. stirringthe mixture was stirred for 45 minutes
  3. customThe reaction mixture was transferred to a separatory funnel
  4. customthe organic layer was separated
  5. dry with materialThe organic portion was dried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. customto yield an oily brown solid
  9. customThe compound was purified by flash chromatography on silica gel (1 L 10% MeOH in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-4f8a21c2c7be40deb0328a99b906535a
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06713474B2

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