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

HRID 1881998Notes

Reaction equation

HRID 1881998 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]([OH:27])=O)=[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=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.[CH3:60][O:61][NH:62][CH3:63]>CN(C)C=O.C(OCC)(=O)C>[OH:1][CH2:2][C:3]1[S:7][C:6]([C:8]2[NH:12][C:11]([CH:13]([C:21]3[CH:22]=[CH:23][C:24]([C:25]([N:62]([O:61][CH3:60])[CH3:63])=[O:27])=[CH:28][CH:29]=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

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 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 593315864-[1-{5-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-1H-pyrrol-2-yl}-2-(tetrahydro-2H-pyran-4-yl)ethyl]-N-methoxy-N-methylbenzamideYield 42%

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 (200 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 (160 μL), and the mixture was stirred for 1% hr. To the reaction mixture was added N-methoxymethanamine hydrochloride (60.0 mg), and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate and washed with 1M hydrochloric acid. The ethyl acetate layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (92.0 mg, yield 42%) was obtained as a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-methanol (19:1, volume ratio). MS: 456 (MH+).

Workup

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

Sources & evidence

ORD record
ord-d7462c72777043adb9d2503f3636cea1
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

Loading…