Acetic Acid → HCID 178480946, Verbindung

HRID 51537

Reaktionsgleichung

Reaktionsgleichung von HRID 51537
[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([CH:12]3[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.C(O)(=O)C.COC(OC)OC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C@H:12]3[CH2:17][CH2:16][C@H:15]([N:23]4[CH2:24][CH2:25][N:20]([CH3:19])[CH2:21][CH2:22]4)[CH2:14][CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 9005Trimethyl orthoformateHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 227364134-(4-Chloro-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-cyclohexanone

Produkt 1

HCID 178480946HCID 178480946, VerbindungAusbeute 24,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 63651,1-DichloroethaneLösungsmittel

Versuchsvorschrift

A mixture of 4-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-cyclohexanone (5.6 g, 14.9 mmol), N-methylpiperazine (3.3 mL, 29.8 mmol), acetic acid (2.6 mL, 44.7 mmol), and trimethylorthoformate (9.9 mL, 89.4 mmol) in dichloroethane (100 mL) was stirred at ambient temperature under an atmosphere of nitrogen for 1 hr. Sodium triacetoxyborohydride (14.2 g, 67.05 mmol) was added into the mixture and stirred at ambient temperature under an atmosphere of nitrogen for 18 hours. The solvent was removed under reduced pressure. The residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The water phase was further extracted with ethyl acetate and the combined organic extracts were dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel using triethylamine/dichloromethane (2:98) followed by methanol/triethylamine/dichloromethane (2:3:95) as mobile phase to yield trans-4-chloro-5-iodo-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidine (1.7 g, 3.7 mmol). 1H NMR (DMSO-d6, 400 MHz) 8.63 (s, 1H), 8.12 (s, 1H), 4.63 (br, 1H), 2.15 (s, 3H), 1.94 (br, 6H), 1.45 (br, 2H) RP-20 HPLC (Hypersil C18, 5 μm, 250×4.6 mm; 25%-100% over 15 min with 0.05 M ammonium acetate, 1 mL/min) Rt 6.17 min.

Aufarbeitung

  1. stirringstirred at ambient temperature under an atmosphere of nitrogen for 18 hours
  2. customThe solvent was removed under reduced pressure
  3. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate
  4. extractionThe water phase was further extracted with ethyl acetate
  5. dry with materialthe combined organic extracts were dried over sodium sulfate
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was purified by flash chromatography on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-77b7e1c130ff4c6882060a79fb95c1e7
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06713474B2

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