Triethylamine → N-methyl-2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-N-[(1R,4S)-1,2,3,4-tetrahydro-4-hydroxy-1-naphthalenyl]-4-thiazolecarboxamide

HRID 2043775ノート

反応式

HRID 2043775 の反応式
[CH3:1][NH:2][C@H:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C@@H:6]([OH:13])[CH2:5][CH2:4]1.C(N(CC)CC)C.[CH3:21][C:22]1[N:26]([CH2:27][C:28]([N:30]2[CH2:35][CH2:34][CH:33]([C:36]3[S:37][CH:38]=[C:39]([C:41](Cl)=[O:42])[N:40]=3)[CH2:32][CH2:31]2)=[O:29])[N:25]=[C:24]([C:44]([F:47])([F:46])[F:45])[CH:23]=1>ClCCl>[CH3:1][N:2]([C@H:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C@@H:6]([OH:13])[CH2:5][CH2:4]1)[C:41]([C:39]1[N:40]=[C:36]([CH:33]2[CH2:34][CH2:35][N:30]([C:28](=[O:29])[CH2:27][N:26]3[C:22]([CH3:21])=[CH:23][C:24]([C:44]([F:45])([F:47])[F:46])=[N:25]3)[CH2:31][CH2:32]2)[S:37][CH:38]=1)=[O:42]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 67461619(1S,4R)-1,2,3,4-tetrahydro-4-(methylamino)-1-naphthalenol2 回HCID 866377272-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarbonyl chloride2 回

生成物 1

HCID 66796075N-methyl-2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-N-[(1R,4S)-1,2,3,4-tetrahydro-4-hydroxy-1-naphthalenyl]-4-thiazolecarboxamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of (1S,4R)-1,2,3,4-tetrahydro-4-(methylamino)-1-naphthalenol and its enantiomer (283 mg, 1.6 mmol) (i.e. the product of Example 26, Step A) and triethylamine (0.5 mL, 3.6 mmol) in 5 mL of dichloromethane was gradually added 2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarbonyl chloride (605 mg, 1.44 mmol) (i.e. the product of Example 19, Step D) at 0° C. The reaction mixture was stirred at room temperature for 1 h, diluted with dichloromethane, and washed with water, 1 N aqueous hydrochloric acid, water, saturated solution of sodium bicarbonate and brine. The filtered reaction mixture was dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by medium-pressure liquid chromatography on silica gel using 0-20% of acetone in ethyl acetate as eluant to give 700 mg of the title compounds, compounds of the present invention as an off-white powder.

後処理

  1. customat 0° C
  2. washwashed with water, 1 N aqueous hydrochloric acid, water, saturated solution of sodium bicarbonate and brine
  3. customThe filtered reaction mixture
  4. dry with materialwas dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by medium-pressure liquid chromatography on silica gel using 0-20% of acetone in ethyl acetate as eluant

出典と根拠

ORDレコード
ord-986254cbb8514f3ea6942f10fb50b8fb
出典データセット
uspto-grants-2013_11
特許番号
US08586611B2

反応ノート

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