Diisopropylethylamine → 2-{[(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl)-6-methoxy-benzoic acid ethyl ester

HRID 8944Notes

Reaction equation

HRID 8944 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[C:45]([C:46]([O:48][CH2:49][CH3:50])=[O:47])=[C:44]([O:51][CH3:52])[CH:43]=[CH:42][CH:41]=1>CC#N>[CH2:49]([O:48][C:46](=[O:47])[C:45]1[C:44]([O:51][CH3:52])=[CH:43][CH:42]=[CH:41][C:40]=1[CH2:39][N:18]([CH2:17][C:9]1[NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:8]=1)[CH:19]1[C:28]2[N:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:22][CH2:21][CH2:20]1)[CH3:50]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 10038926Ethyl 2-bromomethyl-6-methoxybenzoateHCID 219850812-[(5,6,7,8-Tetrahydroquinolin-8-ylamino)-methyl]-benzimidazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 207256252-{[(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl)-6-methoxy-benzoic acid ethyl esterYield 74.8%

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 (0.409 g, 1.08 mmol) in CH3CN (5 mL) was added N,N-diisopropylethylamine (0.38 mL, 2.18 mmol) followed by a solution of ethyl 6-(bromomethyl)-2-methoxybenzoate (0.454 g, 1.66 mmol) in CH3CN (6 mL). The resultant mixture was heated to 60 ° C. for 22 hours then cooled to room temperature. The mixture was concentrated and the residue was partitioned between CH2Cl2 (50 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 (25:1 CH2Cl2—CH3OH) followed a further chromatographic purification by column chromatography on silica gel (2:1 hexanes-EtOAc) and radial chromatography on silica gel (2 mm plate, 100:1:1 CH2Cl2—CH3OH—NH4OH) provided 0.38 g (62%) of a white solid.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between CH2Cl2 (50 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 (25:1 CH2Cl2—CH3OH)
  8. customa further chromatographic purification by column chromatography on silica gel (2:1 hexanes-EtOAc) and radial chromatography on silica gel (2 mm plate, 100:1:1 CH2Cl2—CH3OH—NH4OH)

Sources & evidence

ORD record
ord-95b70511193241adae92e0a25d2fc02a
Source dataset
uspto-grants-2006_08
Patent number
US07091217B2

Reaction notes

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