4-Aminopyridine → HCID 67984089, Verbindung

HRID 2359766Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2359766
[CH3:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[N:9]=2)=[CH:6][N:5]=[C:4]([NH2:21])[N:3]=1.[CH2:22]([O:29]CC(N(OC)C)=O)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.NC1C=CN=CC=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C(OCC1C(C2C=CN=C(S(C)=O)N=2)=CN=C(N)N=1)C1C=CC=CC=1>C1COCC1>[CH2:22]([O:29][CH2:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[N:9]=2)=[CH:6][N:5]=[C:4]([NH2:21])[N:3]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Komponenten

7

Edukt 5

HCID 17274-AminopyridineHCID 2733832Lithium HexamethyldisilazideHCID 114584642-(Benzyloxy)-N-methoxy-N-methylacetamideHCID 67983187HCID 67983187, VerbindungHCID 67983712HCID 67983712, Verbindung

Produkt 1

HCID 67984089HCID 67984089, VerbindungAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

This compound was synthesized in an analogous manner to compound 21 utilizing 2-(benzyloxy)-N-methoxy-N-methylacetamide in step one. To a solution of 4-aminopyridine (79 mg, 0.836 mmol) in THF (1114 μl) cooled to −78° C. was added LHMDS (836 μl, 0.836 mmol). The reaction was stirred −78° C. for 15 minutes, after which time 4′-(benzyloxymethyl)-2-(methylsulfinyl)-4,5′-bipyrimidin-2′-amine (99 mg, 0.279 mmol) was added as a solution in THF (2 mL). The reaction was warmed to rt and stirred for 1 hour. The reaction was quenched by slow addition of saturated ammonium chloride and the reaction mixture was diluted with EtOAc. The residue was then partitioned between water and EtOAc. The organic layer was washed with brine, dried with sodium sulfate, and concentrated in vacuo. The crude product was purified by reverse-phase HPLC [30-100% organic phase over 15 minutes] followed by Biotage™ silica gel chromatography [10 g SNAP column, 100% DCM to 10% MeOH/DCM] to obtain the desired product as a pale yellow solid (94 mg, 88% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.42 (s, 2H) 4.68 (s, 2H) 7.07-7.19 (m, 4H) 7.19-7.31 (m, 4H) 7.76 (d, J=6.57 Hz, 2H) 8.34 (d, J=6.06 Hz, 2H) 8.50-8.64 (m, 2H) 10.05 (s, 1H). HRMS (ES+) for C21H19N7O.H+ [MH+]: calculated, 386.1729; found, 386.1731. UV-LC: 100/100% UV purity at 214/254 nm; tR=2.78 minutes over 7.75 minutes.

Aufarbeitung

  1. temperatureThe reaction was warmed to rt
  2. stirringstirred for 1 hour
  3. customThe reaction was quenched by slow addition of saturated ammonium chloride
  4. additionthe reaction mixture was diluted with EtOAc
  5. customThe residue was then partitioned between water and EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried with sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by reverse-phase HPLC [30-100% organic phase over 15 minutes]

Quellen und Nachweise

ORD-Eintrag
ord-8e22ca554d8d499ebea147106195e741
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08685993B2

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