4-Methylmorpholine → N-cyclopropyl-4-[1-{5-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-1H-pyrrol-2-yl}-2-(tetrahydro-2H-pyran-4-yl)ethyl] benzamide

HRID 1881996Notes

Reaction equation

HRID 1881996 reaction equation
[OH:1][CH2:2][C:3]1[S:7][C:6]([C:8]2[NH:12][C:11]([CH:13]([C:21]3[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:10][CH:9]=2)=[N:5][CH:4]=1.Cl.C(N=C=N[CH2:36][CH2:37][CH2:38][N:39](C)C)C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.C1(N)CC1>CN(C)C=O.C(OCC)(=O)C>[CH:38]1([NH:39][C:25](=[O:26])[C:24]2[CH:23]=[CH:22][C:21]([CH:13]([C:11]3[NH:12][C:8]([C:6]4[S:7][C:3]([CH2:2][OH:1])=[CH:4][N:5]=4)=[CH:9][CH:10]=3)[CH2:14][CH:15]3[CH2:16][CH2:17][O:18][CH2:19][CH2:20]3)=[CH:29][CH:28]=2)[CH2:36][CH2:37]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 593312214-[1-{5-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-1H-pyrrol-2-yl}-2-(tetrahydro-2H-pyran-4-yl)ethyl]benzoic acid

Product 1

HCID 59331538N-cyclopropyl-4-[1-{5-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-1H-pyrrol-2-yl}-2-(tetrahydro-2H-pyran-4-yl)ethyl] benzamideYield 71%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-[1-{5-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-1H-pyrrol-2-yl}-2-(tetrahydro-2H-pyran-4-yl)ethyl]benzoic acid (270 mg) in N,N-dimethylformamide (5 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (140 mg), 1-hydroxybenzotriazole (100 mg) and N-methylmorpholine (215 μL), and the mixture was stirred for 1 hr. To the reaction mixture was added cyclopropylamine (50 μL), and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate and washed with 1M hydrochloric acid. The obtained aqueous layer was neutralized with 1M aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (210 mg, yield 71%) was obtained as a pale-yellow amorphous solid from a fraction eluted with ethyl acetate. MS: 452 (MH+).

Workup

  1. stirringthe mixture was stirred overnight at room temperature
  2. washwashed with 1M hydrochloric acid
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with saturated brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-fb534b72bd724567baddf372c0fe6640
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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