Water → (S)-1-(3-fluoro-benzenesulfonyl)-piperidine-2-carboxylic acid {(S)-2-[4-(3-methoxy-propoxy)-phenyl]-1-methylcarbamoyl-ethyl}-amide

HRID 504164Notes

Reaction equation

HRID 504164 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][NH2:38].C1COCC1.O>ClCCl>[CH3:36][O:35][CH2:34][CH2:33][CH2:32][O:31][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][C@H:20]([NH:19][C:17]([C@@H:12]2[CH2:13][CH2:14][CH2:15][CH2:16][N:11]2[S:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)(=[O:10])=[O:9])=[O:18])[C:21](=[O:22])[NH:38][CH3:37])=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6329MethylamineHCID 8028TetrahydrofuranHCID 66750873(S)-2-{[(S)-1-(3-fluoro-benzenesulfonyl)-piperidine-2-carbonyl]-amino}-3-[4-(3-methoxy-propoxy)-phenyl]-propionic acid

Product 1

HCID 11720781(S)-1-(3-fluoro-benzenesulfonyl)-piperidine-2-carboxylic acid {(S)-2-[4-(3-methoxy-propoxy)-phenyl]-1-methylcarbamoyl-ethyl}-amide

Reagents, catalysts & solvents 1

HCID 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 (3 mL) was added, a 2.0M methyl amine solution in THF (97 μL, 1.9 mmol), PyBoP (87 mg, 0.19 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 35 (34%) mg of (S)-1-(3-fluoro-benzenesulfonyl)-piperidine-2-carboxylic acid {(S)-2-[4-(3-methoxy-propoxy)-phenyl]-1-methylcarbamoyl-ethyl}-amide. LC/MS rt=3.95, 536 m/e (M+H). 1H NMR (300 MHz, dmso-d6) 7.93 (d, J=8.2 Hz, 1H), 7.85 (m, 1H), 7.48-7.37 (m, 4H), 7.11 (d, J=8.3 Hz, 2H), 6.83 (d, J=8.5 Hz, 2H), 4.51 (d, J=4.5 Hz, 1H), 4.25 (m, 1H), 3.95 (t, J=6.5 Hz, 2H), 3.61 (m, 1H), 3.42 (t, J=6.2 Hz, 2H), 3.30-3.21 (m, 5H), 3.15 (m, 1H), 2.90-2.83 (m, 1H), 2.73-2.66 (m, 1H), 2.54 (d, J=4.8 Hz, 3H), 1.95-1.97 (m, 2H), 1.50-1.25 (m, 2H), 1.50-1.05 (m, 2H).

Workup

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

Sources & evidence

ORD record
ord-78a9dc8011d548e6817e13b93b72b996
Source dataset
uspto-grants-2010_08
Patent number
US07777042B2

Reaction notes

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