1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (+/-)-1-Benzyl-N-(3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-N-isobutylpyrrolidine-3-carboxamide

HRID 1024498

Reaction equation

HRID 1024498 reaction equation
Cl[C:2]1[C:7]2[O:8][CH2:9][CH2:10][CH2:11][O:12][C:6]=2[CH:5]=[C:4]([CH2:13][NH:14][CH2:15][CH:16]([CH3:18])[CH3:17])[CH:3]=1.[CH2:19]([N:26]1[CH2:30][CH2:29][CH:28]([C:31]([OH:33])=O)[CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl.C(N=C=NCCCN(C)C)C.CC1C=CN=C(N)C=1C>ClCCl.O>[CH2:19]([N:26]1[CH2:30][CH2:29][CH:28]([C:31]([N:14]([CH2:13][C:4]2[CH:3]=[CH:2][C:7]3[O:8][CH2:9][CH2:10][CH2:11][O:12][C:6]=3[CH:5]=2)[CH2:15][CH:16]([CH3:18])[CH3:17])=[O:33])[CH2:27]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 46173481-benzylpyrrolidine-3-carboxylic AcidHCID 110078842-Amino-3,4-dimethylpyridineHCID 43087680N-(9-chloro-3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-2-methylpropan-1-amine

Product 1

HCID 58080500(+/-)-1-Benzyl-N-(3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-N-isobutylpyrrolidine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

The above amine product, N-(9-chloro-3,4-dihydro-2H-1,5-benzodioxepin-7-ylmethyl)-2-methylpropan-1-amine (807 mg, 3 mmole) was combined with 1-Benzyl-pyrrolidine-3-carboxylic acid (615 mg, 3 mmole) in 50 ml dichloromethane. 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (764 mg, 4 mmole) and dimethyl aminopyridine (562 mg, 4 mmole) were added. The reaction solution was stirred at room temperature overnight. 50 ml of water was added and the mixture was extracted with 50 ml ethyl acetate three times. The organic layer was washed with saturated sodium bicarbonate, water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The product was purified by column chromatography using 50-75% ethyl acetate in hexane. MS (m+1)=457.3; H NMR (500 MHz, CDCl3) 0.95 (m, 6H), 2.00 (m, 1H), 2.05 (m, 1H), 2.15 (m, 1H), 2.25 (m, 1H), 2.55 (m, 1H), 2.65 (m, 1H), 2.90 (m, 1H), 3.00 (m, 1H), 3.10 (d, 1H), 3.15 (m, 1H), 3.25 (d, 1H), 3.40 (m, 1H), 3.75 (m, 2H), 4.30 (m, 4H), 4.45 (s, 1H), 4.55 (d, 1H), 6.6-7.0 (m, 2H), 7.2-7.5 (m, 5H).

Workup

  1. extractionthe mixture was extracted with 50 ml ethyl acetate three times
  2. washThe organic layer was washed with saturated sodium bicarbonate, water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe product was purified by column chromatography

Sources & evidence

ORD record
ord-89263181ac51444aa227ec54a2e8dd11
Source dataset
uspto-grants-2014_05
Patent number
US08722896B2

Linked notes

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