1-Hydroxybenzotriazole → (RS)-1-[2-(4,5-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-hydroxymethyl-thiazol-4-yl]-methanone

HRID 598584ノート

反応式

HRID 598584 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH2:13][OH:14])=[N:10][C:9]=2[C:15]([OH:17])=O)=[CH:4][CH:3]=1.[F:18][C:19]1[C:27]2[N:26]=[C:25]([CH2:28][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][NH:30]3)[NH:24][C:23]=2[CH:22]=[CH:21][C:20]=1[F:35].CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1>CN(C=O)C.C(OCC)C.CO.ClCCl>[F:18][C:19]1[C:27]2[N:26]=[C:25]([CH2:28][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][N:30]3[C:15]([C:9]3[N:10]=[C:11]([CH2:13][OH:14])[S:12][C:8]=3[C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:17])[NH:24][C:23]=2[CH:22]=[CH:21][C:20]=1[F:35]

参加物

8

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 17973676(RS)-4,5-Difluoro-2-piperidin-2-ylmethyl-1H-benzoimidazoleHCID 234501385-(4-Fluoro-phenyl)-2-hydroxymethyl-thiazole-4-carboxylic acid

生成物 1

HCID 66968516(RS)-1-[2-(4,5-Difluoro-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-hydroxymethyl-thiazol-4-yl]-methanone収率 33%

試薬・触媒・溶媒 3

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒HCID 21226129Dichloromethane methanol溶媒

実験手順

A stirring solution of 5-(4-fluoro-phenyl)-2-hydroxymethyl-thiazole-4-carboxylic acid (320 mg, 1.0 mmol, 80% pure) and (RS)-4,5-difluoro-2-piperidin-2-ylmethyl-1H-benzoimidazole, D21 (250 mg, 1.0 mmol) in DMF (10 ml) was treated with EDC.HCl (194 mg, 1.0 mmol) and 1-hydroxybenzotriazole (50 mg, 0.4 mmol). The reaction mixture was stirred at room temperature, under argon for 16 h. The resulting solution was diluted with diethyl ether then washed with saturated aqueous NaHCO3, water (3×) and brine. Drying (MgSO4) and removal of the solvent in vacuo afforded an orange gum. Chromatography (silica gel, 0-2% methanol-dichloromethane) afforded the title compound as an orange powder (160 mg, 33%). Mass spectrum (Electrospray LC/MS) Found 487 (MH+). C24H21F3N4O2S requires 486.

後処理

  1. washthen washed with saturated aqueous NaHCO3, water (3×) and brine
  2. customDrying
  3. custom(MgSO4) and removal of the solvent in vacuo
  4. customafforded an orange gum

出典と根拠

ORDレコード
ord-cbe11634ff8e458e85fde3ad0032b459
出典データセット
uspto-grants-2011_03
特許番号
US07897618B2

反応ノート

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