2-Benzimidazolepropanol → 2-[3-(1H-benzimidazol-2-yl)propoxy]-6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methylpyrimidin-4-amine

HRID 1626364

Reaktionsgleichung

Reaktionsgleichung von HRID 1626364
[Cl:1][C:2]1[N:7]=[C:6](S(C)(=O)=O)[N:5]=[C:4]([NH:12][CH2:13][C:14]2[S:18][C:17]([CH3:19])=[N:16][C:15]=2[CH3:20])[C:3]=1[CH3:21].[NH:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[CH2:31][CH2:32][CH2:33][OH:34].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[NH:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[CH2:31][CH2:32][CH2:33][O:34][C:6]1[N:5]=[C:4]([NH:12][CH2:13][C:14]2[S:18][C:17]([CH3:19])=[N:16][C:15]=2[CH3:20])[C:3]([CH3:21])=[C:2]([Cl:1])[N:7]=1

Komponenten

5

Edukt 3

HCID 754702-BenzimidazolepropanolHCID 2724254Sodium bis(trimethylsilyl)amideHCID 86688161HCID 86688161, Verbindung

Produkt 1

HCID 569494492-[3-(1H-benzimidazol-2-yl)propoxy]-6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methylpyrimidin-4-amineAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methyl-2-methylsulfonyl-pyrimidin-4-amine F5 (480 mg, 1.384 mmol) and 3-(1H-benzimidazol-2-yl)propan-1-ol (244 mg, 1.38 mmol) were placed in a 20 mL vial and dissolved in THF (5 mL). A 1 M solution of NaHMDS in THF (1.38 mL, 1.38 mmol) was added, and the reaction was stirred overnight. Solvent was then removed, and the product was purified by silica gel flash column chromatography (EtOAc/hexanes gradient). 500 mg (82%) of F6 were isolated as an off-white foam. 1H NMR δ (300 MHz, DMSO-d6): 7.84-7.80 (1H, m), 7.76 (2H, dd, J=6.20, 3.18 Hz), 7.51 (2H, dd, J=6.28, 3.15 Hz), 4.46 (2H, d, J=5.76 Hz), 4.37-4.31 (2H, m), 2.54 (4H, s), 2.46 (3H, s), 2.29 (3H, s), 1.99 (3H, s). HRMS (Electrospray): m/z 443.1413 (MH+).

Aufarbeitung

  1. customSolvent was then removed
  2. customthe product was purified by silica gel flash column chromatography (EtOAc/hexanes gradient)

Quellen und Nachweise

ORD-Eintrag
ord-6c502a3edabd4e73a4fcff19328b72c2
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785467B2

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