Reaction #7278

Reaction equation

N′-(1H-benzimidazol-2-ylmethyl)-N′-(5,6,7,8-tetrahydro-8-quinolinyl)-1,4-benzenedimethanamine

N-(tert-butoxycarbonyl)-L-proline

N,N-diisopropylethylamine

1-hydroxybenzotriazole hydrate

1-(3-dimethylaminopropyl)-3-ethyl carbodiimide HCl

→

amide

Yield 116.9%

(S)-Pyrrolidine-2-carboxylic acid 4-{[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzylamide

Yield 116.9%

Solvents

CH2Cl2

sodium bicarbonate

CH2Cl2

Conditions

Workup

1. 1
   Otherthe aqueous layer was separated
2. 2
   Extractionextracted with CH2Cl2 (2×15 mL)
3. 3
   DryingThe combined organic phases were dried (Na2SO4)
4. 4
   Filtrationfiltered
5. 5
   Otherevaporated in vacuo
6. 6
   Otherto give the crude product as a white foam
7. 7
   OtherPurification by column chromatography on silica gel (CH2Cl2/MeOH, 96:4)

Procedure

To a stirred solution of N′-(1H-benzimidazol-2-ylmethyl)-N′-(5,6,7,8-tetrahydro-8-quinolinyl)-1,4-benzenedimethanamine (148 mg, 0.37 mmol) in dry CH2Cl2 (5 mL) was added N-(tert-butoxycarbonyl)-L-proline (88 mg, 0.41 mmol), N,N-diisopropylethylamine (0.13 mL, 0.75 mmol), 1-hydroxybenzotriazole hydrate (68 mg, 0.50 mmol) and 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide HCl (EDC) (99 mg, 0.52 mmol) and the mixture stirred at room temperature overnight. The reaction mixture was diluted with CH2Cl2 (25 mL) and saturated aqueous sodium bicarbonate (30 mL) and the aqueous layer was separated and extracted with CH2Cl2 (2×15 mL). The combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo to give the crude product as a white foam. Purification by column chromatography on silica gel (CH2Cl2/MeOH, 96:4) gave the desired amide (214 mg, 85%) as a white foam.

Source