Morpholine → 5-(morpholin-4-ylcarbonyl)-2-(5-[1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl]-1H-pyrrol-2-yl)pyridine

HRID 1882035Notes

Reaction equation

HRID 1882035 reaction equation
[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([C:21]3[NH:25][C:24]([C:26]4[N:31]=[CH:30][C:29]([C:32](O)=[O:33])=[CH:28][CH:27]=4)=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O.O.C(N(CC)CC)C>[N:35]1([C:32]([C:29]2[CH:28]=[CH:27][C:26]([C:24]3[NH:25][C:21]([CH:13]([C:10]4[CH:11]=[CH:12][C:7]([S:4]([CH:1]5[CH2:2][CH2:3]5)(=[O:5])=[O:6])=[CH:8][CH:9]=4)[CH2:14][CH:15]4[CH2:16][CH2:17][O:18][CH2:19][CH2:20]4)=[CH:22][CH:23]=3)=[N:31][CH:30]=2)=[O:33])[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 593316146-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carboxylic acid

Product 1

HCID 593314975-(morpholin-4-ylcarbonyl)-2-(5-[1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl]-1H-pyrrol-2-yl)pyridineYield 60%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carboxylic acid (0.155 g) in N,N-dimethylformamide (5 mL) were added morpholine (0.056 mL), triethylamine (0.135 mL), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (93 mg) and 1-hydroxybenzotriazole (74 mg), and the mixture was stirred at room temperature for 16 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=40:60-100:0, volume ratio) and recrystallized from hexane-ethyl acetate to give the title compound (0.106 g, yield 60%) as colorless crystals. MS: 550 (MH+). melting point 114-116° C.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed successively with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=40:60-100:0, volume ratio)
  6. customrecrystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-8318784a61e048f9a66e7b29e12f03f4
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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