Diisopropylethylamine → 2-Aminomethyl-5-{[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-phenol

HRID 8918Notes

Reaction equation

HRID 8918 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.C([O:41][C:42]1[CH:47]=[C:46]([CH2:48]Br)[CH:45]=[CH:44][C:43]=1[C:50]#[N:51])(=O)C>CC#N>[NH2:51][CH2:50][C:43]1[CH:44]=[CH:45][C:46]([CH2:48][N:18]([CH2:17][C:9]2[NH:8][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[N:10]=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:47][C:42]=1[OH:41]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 219850812-[(5,6,7,8-Tetrahydroquinolin-8-ylamino)-methyl]-benzimidazole-1-carboxylic acid tert-butyl esterHCID 68619125(5-Bromomethyl-2-cyano-phenyl) acetate

Product 1

HCID 219850692-Aminomethyl-5-{[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-phenolYield 68.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of (1-tert-butoxycarbonyl-1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (0.375 g, 0.99 mmol) in CH3CN (5 mL) was added N,N-diisopropylethylamine (0.35 mL, 2.00 mmol) followed by a solution of (5-bromomethyl-2-cyano-phenyl) acetate (0.318 g, 1.25 mmol) in CH3CN (5 mL). 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—CH30H) followed by radial chromatography on silica gel (2 mm plate, 2:1 hexanes-EtOAc) provided 0.28 g (51%) of a tan 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—CH30H)

Sources & evidence

ORD record
ord-dc4168f35ad440549ee8108f3a2b6374
Source dataset
uspto-grants-2006_08
Patent number
US07091217B2

Reaction notes

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