4-Pyrimidinecarboxylic acid → 1-[1-(9-Methyl-8-pyrimidin-4-yl-9H-purin-6-yl)piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one

HRID 528055

Reaktionsgleichung

Reaktionsgleichung von HRID 528055
[NH2:1][C:2]1[C:3]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=4[NH:18][C:17]3=[O:25])[CH2:12][CH2:11]2)=[N:4][CH:5]=[N:6][C:7]=1[NH:8][CH3:9].CN(C(O[N:34]1N=N[C:36]2[CH:37]=[CH:38][CH:39]=[N:40][C:35]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1C=CC(C(O)=O)=NC=1>CC(N(C)C)=O.C(N(C(C)C)CC)(C)C>[CH3:9][N:8]1[C:36]([C:37]2[CH:38]=[CH:39][N:40]=[CH:35][N:34]=2)=[N:1][C:2]2[C:7]1=[N:6][CH:5]=[N:4][C:3]=2[N:10]1[CH2:11][CH2:12][CH:13]([N:16]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[NH:18][C:17]2=[O:25])[CH2:14][CH2:15]1

Komponenten

6

Edukt 3

HCID 1693064-Pyrimidinecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66802269HCID 66802269, Verbindung

Produkt 1

HCID 668019751-[1-(9-Methyl-8-pyrimidin-4-yl-9H-purin-6-yl)piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-oneAusbeute 5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 31374DimethylacetamideLösungsmittelHCID 81531DiisopropylethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a solution of 1-(1-(5-amino-6-(methylamino)pyrimidin-4-yl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one (50 mg, 0.14 mmol) in anhydrous DMA (5 mL) and diisopropylethylamine (0.5 mL) were added HATU (150 mg, 0.39 mmol), and pyrimidine-4-carboxylic acid (100 mg, 0.8 mmol). The reaction mixture was stirred for 1 h, and concentrated under reduced pressure. The resulting oil was dissolved in 10 mL of dichloromethane, and the solution was washed with 5 mL of water. The organic layer was dried over MgSO4, concentrated under reduced pressure, and the residue was dissolved in Acetic acid (2 mL). The reaction mixture was heated in a microwave reactor to 150° C. for 20 min, and concentrated under reduced pressure. The product was purified by preparatory HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid) to give 3 mg of the title compound. 1H NMR (400 MHz, DMSO-d6): δ 10.85 (s, 1H), 9.34 (s, 1H), 8.96 (d, 1H), 8.36 (s, 1H), 8.27 (d, 1H), 7.21-7.14 (m, 1H), 6.93 (d, 3H), 4.64-4.52 (m, 1H), 4.18 (s, 3H), 2.37 (dd, 2H), 1.85 (t, 2H); MS (EI) for C23H21N9O: 428.4 (MH+).

Aufarbeitung

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe resulting oil was dissolved in 10 mL of dichloromethane
  3. washthe solution was washed with 5 mL of water
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. dissolutionthe residue was dissolved in Acetic acid (2 mL)
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified by preparatory HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid)

Quellen und Nachweise

ORD-Eintrag
ord-aaf78d41a2c94ac181a12b073d4a929b
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346807B2

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