2-Chloropyridin-4-amine → Vps34-IN-1

HRID 1397147Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1397147
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([Cl:8])[CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH:19]1([CH2:22][C:23]2[C:28]([C:29]3[CH:34]=[CH:33][N:32]=[C:31](S(C)=O)[N:30]=3)=[CH:27][N:26]=[C:25]([NH:38][CH2:39][C:40]([CH3:43])([OH:42])[CH3:41])[N:24]=2)[CH2:21][CH2:20]1>C1COCC1>[Cl:8][C:4]1[CH:3]=[C:2]([NH:1][C:31]2[N:30]=[C:29]([C:28]3[C:23]([CH2:22][CH:19]4[CH2:21][CH2:20]4)=[N:24][C:25]([NH:38][CH2:39][C:40]([CH3:43])([OH:42])[CH3:41])=[N:26][CH:27]=3)[CH:34]=[CH:33][N:32]=2)[CH:7]=[CH:6][N:5]=1

Komponenten

5

Edukt 3

HCID 844322-Chloropyridin-4-amineHCID 2733832Lithium HexamethyldisilazideHCID 679836401-(4'-(Cyclopropylmethyl)-2-(methylsulfinyl)-4,5'-bipyrimidin-2'-ylamino)-2-methylpropan-2-ol

Produkt 1

HCID 57404276Vps34-IN-1Ausbeute 49,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 4-amino-2-chloropyridine (53.3 mg, 0.415 mmol) in THF (277 μl) cooled to −78° C. under nitrogen, LiHMDS (415 μl, 0.415 mmol) was added dropwise. The reaction mixture was warmed up to rt, then was stirred for 30 min. To the reaction mixture cooled back to −78° C., 1-(4′-(cyclopropylmethyl)-2-(methylsulfinyl)-4,5′-bipyrimidin-2′-ylamino)-2-methylpropan-2-ol (5-3) (50 mg, 0.138 mmol) was added, and the reaction mixture was warmed up to rt, then was stirred for additional 1 h. According to LC/MS, the reaction was complete. The crude product was purified by reverse-phase HPLC [30-100% organic phase over 15 min] followed by Biotage silica gel chromatography [10 g SNAP column, 100% DCM to 12% MeOH/DCM] to obtain the desired product (29 mg, 49%).

Aufarbeitung

  1. temperatureTo the reaction mixture cooled back to −78° C.
  2. temperaturethe reaction mixture was warmed up to rt
  3. stirringwas stirred for additional 1 h
  4. customThe crude product was purified by reverse-phase HPLC [30-100% organic phase over 15 min]

Quellen und Nachweise

ORD-Eintrag
ord-2ca5b94e327742c8b0f7c6ee5a0e21d9
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901147B2

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