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 1881998ノート

反応式

HRID 1881998 の反応式
[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

参加物

8

反応物 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

生成物 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-methylbenzamide収率 42%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-d7462c72777043adb9d2503f3636cea1
出典データセット
uspto-grants-2012_11
特許番号
US08318746B2

反応ノート

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