Diisopropylethylamine → (S)-N-methyl-6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinamide

HRID 2077828Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2077828
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19]4[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][N:20]=4)[CH2:15][CH2:14]3)[CH:10]=[N:11][C:5]=2[N:4]2[CH2:28][CH2:29][CH2:30][C@@H:3]12.C[CH2:32][N:33](C(C)C)C(C)C.Cl.CN.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CO>[CH3:32][NH:33][C:23](=[O:24])[C:22]1[CH:26]=[CH:27][C:19]([N:16]2[CH2:17][CH2:18][N:13]([CH2:12][C:9]3[CH:10]=[N:11][C:5]4[N:4]5[CH2:28][CH2:29][CH2:30][C@H:3]5[C:2](=[O:1])[NH:7][C:6]=4[CH:8]=3)[CH2:14][CH2:15]2)=[N:20][CH:21]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58324509(S)-6-(4((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinic acid

Produkt 1

HCID 58324370(S)-N-methyl-6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinamideAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(S)-6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinic acid (100 mg, 0.245 mmol) was suspended in DMF (1.5 mL) and DIPEA (0.3 mL) was added followed by methylamine hydrochloride (27 mg, 0.400 mmol) and HATU (200 mg, 0.526 mmol). The reaction mixture was stirred at ambient temperature for 4 h and diluted with MeOH (2 mL). The solution was purified using HPCL (25-95% acetonitrile in water, NH4HCO3 buffered). The fractions were concentrated in vacuo and the resulting residue was crystallized with MeOH-water (1:5, 15 mL) to afford the title compound as an off-white solid (52.3 mg, 51%). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 1.80-2.03 (m, 3H) 2.09-2.25 (m, 1H) 2.41 (br. s., 4H) 2.74 (d, J=4.29 Hz, 3H) 3.34-3.44 (m, 3H) 3.46-3.64 (m, 5H) 3.92-4.05 (m, 1H) 6.82 (d, J=9.09 Hz, 1H) 6.99 (d, 1H) 6.93-7.04 (m, 1H) 7.61 (s, 1H) 7.91 (dd, J=8.97, 2.15 Hz, 1H) 8.17-8.23 (m, 1H) 8.56 (d, J=1.77 Hz, 1H) 10.44 (s, 1H); [M+H] calc'd for C22H27N7O2, 422; found, 422.

Aufarbeitung

  1. customThe solution was purified
  2. concentrationThe fractions were concentrated in vacuo
  3. customthe resulting residue was crystallized with MeOH-water (1:5, 15 mL)

Quellen und Nachweise

ORD-Eintrag
ord-3e93fb3aef774d4ea6447b3c8232644a
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07928105B2

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