Lithium Hydroxide → n-[(1,3-Benzodioxol-5-yl)methyl]-1-[2-(1h-imidazol-1-yl)pyrimidin-4-yl]indole-6-carboxamide

HRID 1760430

Reaktionsgleichung

Reaktionsgleichung von HRID 1760430
[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][CH:2]=1.[Li+].[OH-].CN(C(ON1N=[N:24][C:19]2C=C[CH:22]=[N:23][C:18]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC[N:35]([CH:39]([CH3:41])C)[CH:36]([CH3:38])[CH3:37].[CH2:42]([NH2:52])[C:43]1[CH:51]=[CH:50][C:49]2[O:48][CH2:47][O:46][C:45]=2[CH:44]=1.[CH2:53]1[CH2:57][O:56][CH2:55][CH2:54]1.O>>[O:48]1[C:49]2[CH:50]=[CH:51][C:43]([CH2:42][NH:52][C:55]([C:54]3[CH:37]=[C:36]4[C:38]([CH:41]=[CH:39][N:35]4[C:6]4[CH:5]=[CH:4][N:3]=[C:2]([N:23]5[CH:18]=[CH:19][N:24]=[CH:22]5)[N:1]=4)=[CH:57][CH:53]=3)=[O:56])=[CH:44][C:45]=2[O:46][CH2:47]1

Komponenten

7

Edukt 6

HCID 3939Lithium HydroxideHCID 9260PyrimidineHCID 75799Benzo-1,3-dioxole-5-methylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21881883Oxolane--water (1/1)

Produkt 1

HCID 22487625n-[(1,3-Benzodioxol-5-yl)methyl]-1-[2-(1h-imidazol-1-yl)pyrimidin-4-yl]indole-6-carboxamideAusbeute 4 %

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of indole-5-carboxylic acid (0.50 g, 3.1 mmol) in MeOH (25 mL) was added trimethylsilyldiazomethane until no gas evolution was observed. The solution was concentrated, dissolved in CH2Cl2, and washed with saturated NaHCO3 and brine. The organic layer was dried (MgSO4) and the solvent was removed in vacuo to give 0.54 g of the ester (1H NMR (CDCl3) δ 3.95 (s, 3), 6.63 (s, 1), 7.25 (m, 1), 7.40 (d, 1), 7.95 (d, 1), 8.25-8.4 (br s, 1), 8.45 (s, 1)). The ester (100 mg, 0.58 mmol) was dissolved in DMF (10 mL) and 4-chloro-2-imidazol-1-ylpyrimidine (113 mg, 0.63 mmol) was added. After heating at 60° C. for 18 hours, the solvent was removed in vacuo, the residue was dissolved in CH2Cl2, and washed with saturated NaHCO3 and brine. The organic layer was dried (MgSO4), the solvent was removed in vacuo and the residue was chromatographed (CH2Cl2/MeOH, 19/1) to give 68 mg (37%) of the pyrimidine (1H NMR (CDCl3) δ 3.95 (s, 3), 6.90 (s, 1), 7.25 (m, 2), 7.80 (m, 1), 7.95 (s, 1), 8.10 (d, 1), 8.4 (s, 1), 8.50 (d, 1), 8.70 (m, 2)). The pyrimidine was dissolved in THF/water (1/1) and LiOH (6 mg, 0.21 mmol) was added. After heating at 60° C. for 3 hours, the solvent was removed in vacuo and acidified with methanolic HCl. The solvent was removed in vacuo, dissolved in DMF and treated with HATU (42 mg, 0.11 mmol), DIEA (37 mg, 0.21 mmol), and piperonylamine (26 mL, 0.21 mmol). After stirring for 18 hours, the solvent was removed in vacuo, the residue was dissolved in CH2Cl2, and washed with saturated NaHCO3 and brine. The organic layer was dried (MgSO4), the solvent was removed in vacuo, and the residue was chromatographed (CH2Cl2/MeOH, 19/1) to give 2 mg (4%) of N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]indole-6-carboxamide; 1H NMR (CDCl3) δ 3.75 (s, 2), 5.95 (s, 2), 6.80-6.90 (m, 2), 7.05-7.15 (m, 2), 7.25 (m, 2), 7.75-7.85 (m, 2), 8.00 (s, 2), 8.50-8.60 (m, 2), 8.70-8.80 (m, 1); MS: (439.2 M+H)+.

Aufarbeitung

  1. customthe solvent was removed in vacuo
  2. customThe solvent was removed in vacuo
  3. dissolutiondissolved in DMF
  4. customthe solvent was removed in vacuo
  5. dissolutionthe residue was dissolved in CH2Cl2
  6. washwashed with saturated NaHCO3 and brine
  7. dry with materialThe organic layer was dried (MgSO4)
  8. customthe solvent was removed in vacuo
  9. customthe residue was chromatographed (CH2Cl2/MeOH, 19/1)

Quellen und Nachweise

ORD-Eintrag
ord-755f52ee2d1e43a2b3f10677f58d216c
Quelldatensatz
uspto-grants-2005_01
Patentnummer
US06841673B2

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