1-(Pyridin-2-yl)ethan-1-amine → 2-[(1-Pyridin-2-yl-ethylamino)-methyl]-2,3-dihydro-benzoimidazole-1-carboxylic acid tert-butyl ester

HRID 251253

Reaktionsgleichung

Reaktionsgleichung von HRID 251253
O.[OH-].[Cs+].[N:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]([NH2:12])[CH3:11].[C:13]([O:17][C:18]([N:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[N:22]=[C:21]1[CH2:29]Cl)=[O:19])([CH3:16])([CH3:15])[CH3:14]>CN(C1C=CN=CC=1)C.CN(C=O)C>[C:13]([O:17][C:18]([N:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[NH:22][CH:21]1[CH2:29][NH:12][CH:10]([C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][N:4]=1)[CH3:11])=[O:19])([CH3:16])([CH3:14])[CH3:15]

Komponenten

6

Edukt 3

HCID 5418771-(Pyridin-2-yl)ethan-1-amineHCID 15829159tert-Butyl 2-(chloromethyl)-1H-benzimidazole-1-carboxylateHCID 23679066Caesium hydroxide--water (1/1/1)

Produkt 1

HCID 672726842-[(1-Pyridin-2-yl-ethylamino)-methyl]-2,3-dihydro-benzoimidazole-1-carboxylic acid tert-butyl esterAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a suspension of crushed and dried 3 A molecular sieves (1.0393 g) in DMF (15 mL) was added cesium hydroxide monohydrate (0.6272 g, 3.7 mmol) and DMAP (0.0366 g, 0.3 mmol), and the mixture was stirred at room temperature for 15 minutes. To this was added 1-pyridin-2-yl-ethylamine (0.4168 g, 3.4 mmol) in DMF (10 mL), and was stirred for 30 minutes. Then 2-chloromethyl-benzoimidazole-1-carboxylic acid tert-butyl ester (1.1050 g, 4.1 mmol) was added and the reaction was stirred at room temperature for 19 hours. The reaction mixture was filtered with CH2Cl2, concentrated, and diluted with 1N NaOH (75 mL) and CH2Cl2 (100 mL). The layers were separated and the aqueous phase was extracted with CH2Cl2 (4×150 mL). The combined organic layers were washed with brine (1×100 mL), dried (Na2SO4), and concentrated. Purification of the crude material by column chromatography on silica gel (33:1:1 CH2Cl2-MeOH—NH4OH) provided 0.7260 g (61%) of 2-[(1-pyridin-2-yl-ethylamino)-methyl]-2,3-dihydro-benzoimidazole-1-carboxylic acid tert-butyl ester as an orange oil. 1H NMR (CDCl3) δ 1.47 (d, 3H, J=6.0 Hz), 1.66 (s, 9H), 2.92 (d, 2H, J=31.0 Hz), 4.00-4.07 (m, 1H), 4.13-4.29 (m, 1H), 7.03-7.04 (m, 1H), 7.27-7.33 (m, 3H), 7.48-7.55 (m, 1H), 7.65-7.70 (m, 1H), 7.82-7.86 (m, 1H), 8.48 (d, 1H, J=4.8 Hz).

Aufarbeitung

  1. additionTo a suspension
  2. customof crushed
  3. dry with materialdried 3 A molecular sieves (1.0393 g) in DMF (15 mL)
  4. stirringwas stirred for 30 minutes
  5. stirringthe reaction was stirred at room temperature for 19 hours
  6. filtrationThe reaction mixture was filtered with CH2Cl2
  7. concentrationconcentrated
  8. additiondiluted with 1N NaOH (75 mL) and CH2Cl2 (100 mL)
  9. customThe layers were separated
  10. extractionthe aqueous phase was extracted with CH2Cl2 (4×150 mL)
  11. washThe combined organic layers were washed with brine (1×100 mL)
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated
  14. customPurification of the crude material by column chromatography on silica gel (33:1:1 CH2Cl2-MeOH—NH4OH)

Quellen und Nachweise

ORD-Eintrag
ord-96b5bd2d5f494aef9a68fa723e82dbc3
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863293B2

Verknüpfte Notizen

Wird geladen…