Morpholine → HCID 58355214, compound

HRID 2168937Notes

Reaction equation

HRID 2168937 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[CH2:45][CH2:44][O: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]([CH3:17])[CH3:18])[C@H:12]3[CH2:11][C@@H:10]([C:37]([N:40]4[CH2:45][CH2:44][O: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 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58355276HCID 58355276, compound

Product 1

HCID 58355214HCID 58355214, 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 (207 mg), morpholine (87 μl), HOBt (40 mg) and triethylamine (210 μl) were dissolved in DMF (10 ml), WSC.HCl (180 mg) 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 (1:9)-ethyl acetate was concentrated under reduced pressure to give the object product (160 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 (1:9)-ethyl acetate
  7. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-bb603b7630134968b05e32d58559ccf8
Source dataset
uspto-grants-2015_06
Patent number
US09045436B2

Reaction notes

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