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 1592660Notes

Reaction equation

HRID 1592660 reaction equation
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]

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a suspension of crushed and dried 3A 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).

Workup

  1. additionTo a suspension
  2. customof crushed
  3. dry with materialdried 3A 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)

Sources & evidence

ORD record
ord-ad368dc97d904c5ba2c4e80031f8c37b
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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