Diisopropylethylamine → (4-Aminomethyl-3-methoxy-benzyl)-(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine

HRID 1157863Notes

Reaction equation

HRID 1157863 reaction equation
C(OC([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[CH2:17][NH:18][CH:19]1[C:28]2[N:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:22][CH2:21][CH2:20]1)=O)(C)(C)C.C(N(CC)C(C)C)(C)C.Br[CH2:39][C:40]1[CH:47]=[CH:46][C:43]([C:44]#[N:45])=[C:42]([O:48][CH3:49])[CH:41]=1>CC#N>[NH2:45][CH2:44][C:43]1[CH:46]=[CH:47][C:40]([CH2:39][N:18]([CH2:17][C:9]2[NH:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:8]=2)[CH:19]2[C:28]3[N:27]=[CH:26][CH:25]=[CH:24][C:23]=3[CH2:22][CH2:21][CH2:20]2)=[CH:41][C:42]=1[O:48][CH3:49]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 219850074-(Bromomethyl)-2-methoxybenzonitrileHCID 219850812-[(5,6,7,8-Tetrahydroquinolin-8-ylamino)-methyl]-benzimidazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 21985083(4-Aminomethyl-3-methoxy-benzyl)-(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amineYield 68.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (1-tert-butoxycarbonyl-1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (0.386 g, 1.02 mmol) in CH3CN (10 mL) was added N,N-diisopropylethylamine (0.35 mL, 2.00 mmol) followed by of 4-(bromomethyl)-2-methoxybenzonitrile (0.363 g, 1.60 mmol). The resultant mixture was heated to 60° C. for 15 hours then cooled to room temperature. The mixture was concentrated and the residue was partitioned between CH2Cl2 (40 mL) and brine (10 mL). The phases were separated and the aqueous phase was extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:1 CH2Cl2—CH3OH) followed by radial chromatography on silica gel (2 mm plate, 2:1 hexanes-EtOAc) provided 0.30 g (56%) of a white foam.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between CH2Cl2 (40 mL) and brine (10 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with CH2Cl2 (3×10 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography on silica gel (20:1 CH2Cl2—CH3OH)

Sources & evidence

ORD record
ord-32a5df0f10a24fd0885d2d2ab9113a37
Source dataset
uspto-grants-2010_10
Patent number
US07807694B2

Reaction notes

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