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

HRID 7182

Reaction equation

HRID 7182 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH:21]1[C:30]2[N:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH2:24][CH2:23][CH2:22]1)[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][NH2:20])=[CH:15][CH:14]=1.C(OC([N:38]1[CH2:45][CH2:44][CH2:43][C@H:39]1[C:40](O)=[O:41])=O)(C)(C)C.C(N(CC)C(C)C)(C)C.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.C(=O)(O)[O-].[Na+]>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH2:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:19][NH:20][C:40]([C@@H:39]2[CH2:43][CH2:44][CH2:45][NH:38]2)=[O:41])=[CH:17][CH:18]=1)[CH:21]1[C:30]2[N:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH2:24][CH2:23][CH2:22]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 21985008N-[(1H-Benzo[d]imidazol-2-yl)methyl]-N-(4-(aminomethyl)-benzyl)-5,6,7,8-tetrahydroquinolin-8-amine

Product 1

HCID 59989987(s)-Pyrrolidine-2-carboxylic acid 4-{[(1h-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzylamideYield 116.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

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.

Workup

  1. customthe aqueous layer was separated
  2. extractionextracted with CH2Cl2 (2×15 mL)
  3. dry with materialThe combined organic phases were dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto give the crude product as a white foam
  7. customPurification by column chromatography on silica gel (CH2Cl2/MeOH, 96:4)

Sources & evidence

ORD record
ord-31bd20a9662e4534960e36dc214e3c85
Source dataset
uspto-grants-2006_08
Patent number
US07084155B2

Linked notes

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