(2-Thienylmethyl)amine → HCID 68226586, Verbindung

HRID 1186521Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1186521
CS([C:5]1[N:10]=[C:9]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([N:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)[C:14]3=[N:13][CH:12]=2)[CH:8]=[CH:7][N:6]=1)(=O)=O.[S:27]1[CH:31]=[CH:30][CH:29]=[C:28]1[CH2:32][NH2:33]>>[CH3:26][N:23]1[CH2:24][CH2:25][N:20]([C:19]2[C:14]3[N:15]([C:11]([C:9]4[CH:8]=[CH:7][N:6]=[C:5]([NH:33][CH2:32][C:28]5[S:27][CH:31]=[CH:30][CH:29]=5)[N:10]=4)=[CH:12][N:13]=3)[CH:16]=[CH:17][N:18]=2)[CH2:21][CH2:22]1

Komponenten

3

Edukt 2

HCID 34005(2-Thienylmethyl)amineHCID 682264863-(2-Methanesulfonyl-pyrimidin-4-yl)-8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazine

Produkt 1

HCID 68226586HCID 68226586, Verbindung

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

The mixture of 3-(2-methanesulfonyl-pyrimidin-4-yl)-8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazine (from Example 46 supra) (150 mg, 0.402 mmol) and thiophen-2-ylmethanamine (182 mg, 1.608 mmol) was heated at 140° C. with stirring for 2 hours. The oil was purified by chromatography (silica gel, 10 g, 200-300 mesh, eluting with dichloromethane:methanol, 30:1 to 10:1) to afford the crude product (115 mg). The crude product was purified by prep-HPLC. Several drops of concentrated HCl were added to the fractions with product. After sonicating for several minutes, solution was concentrated under reduced pressure to afford {4-[8-(4-methyl-piperazin-1-yl)-imidazo [1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-thiophen-2-ylmethyl-amine; hydrochloride. (Yield 34 mg, 21.2%). 1H NMR (300 MHz, CD3OD): δ 9.02 (brs, 1H), 8.84 (s, 1H), 8.39 (d, 1H, J=6.3 Hz), 7.69-7.63 (m, 2H), 7.40 (brs, 1H), 7.23 (s, 1H), 7.06-7.03 (m, 1H), 5.62-5.51 (m, 2H), 5.06-4.99 (m, 2H), 3.88-3.75 (m, 4H), 3.48-3.37 (m, 2H), 3.00 (s, 3H). LC-MS: [M+H]+ 407.

Aufarbeitung

  1. customThe oil was purified by chromatography (silica gel, 10 g, 200-300 mesh, eluting with dichloromethane:methanol, 30:1 to 10:1)
  2. customto afford the crude product (115 mg)
  3. customThe crude product was purified by prep-HPLC
  4. additionSeveral drops of concentrated HCl were added to the fractions with product
  5. customAfter sonicating for several minutes
  6. concentrationsolution was concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-bbdc49f280f1492d923239d026ed842d
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08673905B2

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