1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (S)-1-(3-fluoro-benzenesulfonyl)-piperidine-2-carboxylic acid {(S)-1-((S)-2-methoxy-1-methyl-ethylcarbamoyl)-2-[4-(3-methoxy-propoxy)-phenyl]-ethyl}-amide

HRID 504165Notes

Reaction equation

HRID 504165 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([S:8]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]2[C:17]([NH:19][C@@H:20]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][CH2:34][O:35][CH3:36])=[CH:27][CH:26]=2)[C:21](O)=[O:22])=[O:18])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[CH3:37][O:38][CH2:39][C@@H:40]([NH2:42])[CH3:41].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.O>[CH3:37][O:38][CH2:39][C@@H:40]([NH:42][C:21]([C@@H:20]([NH:19][C:17]([C@@H:12]1[CH2:13][CH2:14][CH2:15][CH2:16][N:11]1[S:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1)(=[O:10])=[O:9])=[O:18])[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][CH2:34][O:35][CH3:36])=[CH:27][CH:26]=1)=[O:22])[CH3:41]

Participants

7

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 70215362-Propanamine, 1-methoxy-, (2S)-HCID 66750873(S)-2-{[(S)-1-(3-fluoro-benzenesulfonyl)-piperidine-2-carbonyl]-amino}-3-[4-(3-methoxy-propoxy)-phenyl]-propionic acid

Product 1

HCID 59428651(S)-1-(3-fluoro-benzenesulfonyl)-piperidine-2-carboxylic acid {(S)-1-((S)-2-methoxy-1-methyl-ethylcarbamoyl)-2-[4-(3-methoxy-propoxy)-phenyl]-ethyl}-amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To (S)-2-{[(S)-1-(3-fluoro-benzenesulfonyl)-piperidine-2-carbonyl]-amino}-3-[4-(3-methoxy-propoxy)-phenyl]-propionic acid (98 mg, 0.19 mmol) in dichloromethane (2 mL) was added 2-methoxy-1-(S)-methyl ethyl amine (19 mg, 0.19 mmol), 1-hydroxybenzotriazole hydrate (36 mg, 0.27 mol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (47 mg, 0.25 mmol) at room temperature. Upon reaction completion water was added. The mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. The residue was chromatographed on silica gel (dichloromethane/ethyl acetate, 80/20 as eluant) to produce 87 (77%) mg of (S)-1-(3-fluoro-benzenesulfonyl)-piperidine-2-carboxylic acid {(S)-1-((S)-2-methoxy-1-methyl-ethylcarbamoyl)-2-[4-(3-methoxy-propoxy)-phenyl]-ethyl}-amide. LC/MS rt=3.95, 536 m/e (M+H). 1H NMR (300 MHz, dmso-d6) 7.90 (d, J=8 Hz, 1H), 7.76 (d, J=8 Hz, 1H), 7.48-7.37 (m, 4H), 7.13 (d, J=8.5 Hz, 2H), 6.83 (d, J=8.5 Hz, 2H), 4.50 (m, 1H), 4.28 (m, 1H), 3.96 (t, J=6.4 Hz, 2H), 3.79 (m, 1H), 3.63 (m, 1H), 3.42 (t, J=6.2 Hz, 2H), 3.30-3.21 (m, 9H), 3.17-3.05 (m, 2H), 3.90-3.82 (m, 1H), 3.75-3.65 (m, 1H), 1.98-1.85 (m, 2H), 1.45-1.10 (m, 4H), 1.00 (d, J=6.7 Hz, 3H).

Workup

  1. additionwas added
  2. extractionThe mixture was extracted with ethyl acetate
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel (dichloromethane/ethyl acetate, 80/20 as eluant)

Sources & evidence

ORD record
ord-d8b4f9f684774c4d83d78780a2a1bbd3
Source dataset
uspto-grants-2010_08
Patent number
US07777042B2

Reaction notes

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