Pyrrolidine → HCID 58355758, compound

HRID 1259948Notes

Reaction equation

HRID 1259948 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([N:14]([C:19]([C:21]2[N:25]([CH2:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[C:24]3[C:32]([F:36])=[CH:33][CH:34]=[CH:35][C:23]=3[N:22]=2)=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:11][C@@H:10]([C:37](O)=[O:38])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:40]1[CH2:44][CH2:43][CH2:42][CH2:41]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.C(N(CC)CC)C>[F:36][C:32]1[C:24]2[N:25]([CH2:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[C:21]([C:19]([N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C@H:12]3[CH2:11][C@@H:10]([C:37]([N:40]4[CH2:44][CH2:43][CH2:42][CH2:41]4)=[O:38])[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:13]3)=[O:20])=[N:22][C:23]=2[CH:35]=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58355276HCID 58355276, compound

Product 1

HCID 58355758HCID 58355758, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

(3R,5S)-1-(tert-Butoxycarbonyl)-5-[{[7-fluoro-1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid (1.65 g), pyrrolidine (500 μl), HOBt (270 mg) and triethylamine (1.27 ml) were dissolved in DMF (50 ml), WSC.HCl (1.15 g) was added, and the mixture was stirred at 50° C. for 1 hr. The reaction mixture was concentrated under reduced pressure, diluted with saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (5:95)-ethyl acetate-ethyl acetate-methanol (9:1) was concentrated under reduced pressure to give the object product (170 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with saturated aqueous sodium hydrogen carbonate
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialThe extract was dried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. washa fraction eluted with ethyl acetate-hexane (5:95)-ethyl acetate-ethyl acetate-methanol (9:1)
  7. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-1808c027e4234f82a2d579f576f35f4f
Source dataset
uspto-grants-2013_06
Patent number
US08466282B2

Reaction notes

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