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 2043775노트

반응식

HRID 2043775 반응식
[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]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 67461619(1S,4R)-1,2,3,4-tetrahydro-4-(methylamino)-1-naphthalenol2회HCID 866377272-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarbonyl chloride2회

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-986254cbb8514f3ea6942f10fb50b8fb
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08586611B2

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