Diisopropylethylamine → HCID 68461104, compound

HRID 502567Notes

Reaction equation

HRID 502567 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([NH:10][CH2:11][CH2:12][CH2:13][NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)=[N:2]1.[C:30]([O:34][C:35]([N:37]1[CH2:41][CH2:40][CH2:39][CH:38]1[CH2:42][C:43](O)=[O:44])=[O:36])([CH3:33])([CH3:32])[CH3:31].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([NH:10][CH2:11][CH2:12][CH2:13][N:14]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)[C:43](=[O:44])[CH2:42][CH:38]2[CH2:39][CH2:40][CH2:41][N:37]2[C:35]([O:34][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:36])=[N:2]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 40183572-{1-[(Tert-butoxy)carbonyl]pyrrolidin-2-yl}acetic acidHCID 58726830N1-(benzo[d]isothiazol-3-yl)-N3-((4'-methoxybiphenyl-4-yl)methyl)propane-1,3-diamine

Product 1

HCID 68461104HCID 68461104, compoundYield 19.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N1-(Benzo[d]isothiazol-3-yl)-N3-((4′-methoxybiphenyl-4-yl)methyl)propane-1,3-diamine (100 mg, 0.25 mmol), 2-carboxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (68 mg, 0.34 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarboduimide hydrochloride (58 mg, 0.30 mmol) were dissolved in anhydrous methylene chloride (10 mL). Diisopropylethylamine (52 μL, mmol) added to the mixture. The reaction was allowed to stir overnight at room temperature. The solution was washed with water, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by column chromatography, on silica gel, eluting with a mixture of 3:1 hexanes:ethyl acetate yielded tert-butyl 2-(2-((3-(benzo[d]isothiazol-3-ylamino)propyl)((4′-methoxybiphenyl-4-yl)methyl)amino)-2-oxoethyl)pyrrolidine-1-carboxylate as a solid (30 mg). 1H NMR (300 MHz, CDCl3): 7.90-7.95 (m, 1H), 7.75-7.85 (m, 1H), 7.35-7.55 (m, 6H), 7.19-7.25 (m, 2H), 6.95-7.00 m, 2H), 4.90-5.00 (m, 1H), 4.55-4.65 (m, 2H), 4.19-4.25 (m, 1H), 3.85 (s, 3H), 3.55-3.65 (m, 2H), 3.30-3.35 (m, 2H), 3.10-3.19 (m, 1H), 2.35-2.45 (m, 1H), 2.05-2.15 (m, 1H), 1.80-1.90 (m, 4H), 1.50 ppm (s, 9H). MW=615 confirmed by LC-MS, tr=5.12 min (Method B) MH+=614-616.

Workup

  1. washThe solution was washed with water
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customPurification by column chromatography
  5. washon silica gel, eluting with a mixture of 3:1 hexanes

Sources & evidence

ORD record
ord-15622b9a75c248ca8b59d3ff43bd9688
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

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