Triethylamine → 6-[4-[4-[2-[4-(Methylsulfonyl)piperazin-1-yl]ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

HRID 1675158ノート

反応式

HRID 1675158 の反応式
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[N:6]1([CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([CH:21]3[CH2:26][CH2:25][N:24]([C:27]4[CH:28]=[CH:29][C:30]5[N:31]([C:33]([C:36]([F:39])([F:38])[F:37])=[N:34][N:35]=5)[N:32]=4)[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1.C(N(CC)CC)C>C(Cl)Cl.O>[CH3:1][S:2]([N:9]1[CH2:10][CH2:11][N:6]([CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([CH:21]3[CH2:26][CH2:25][N:24]([C:27]4[CH:28]=[CH:29][C:30]5[N:31]([C:33]([C:36]([F:39])([F:37])[F:38])=[N:34][N:35]=5)[N:32]=4)[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[CH2:7][CH2:8]1)(=[O:4])=[O:3]

参加物

6

反応物 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 667881436-[4-[4-(2-Piperazin-1-ylethoxy)phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

生成物 1

HCID 591497976-[4-[4-[2-[4-(Methylsulfonyl)piperazin-1-yl]ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine収率 60%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

A solution of methanesulfonyl chloride (0.034 mL, 0.44 mmol) in DCM (0.5 mL) was added dropwise to 6-[4-[4-(2-piperazin-1-ylethoxy)phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (obtained as described in Example 727) (175 mg, 0.37 mmol) and triethylamine (0.103 mL, 0.74 mmol) in DCM (1 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 5 minutes then allowed to warm to room temperature and stirred for a further 15 minutes. The reaction mixture was diluted with water (2 mL), passed through a phase separating cartridge then the organic layer evaporated to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 6-[4-[4-[2-[4-(methylsulfonyl)piperazin-1-yl]ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (122 mg, 60%).

後処理

  1. temperatureto warm to room temperature
  2. stirringstirred for a further 15 minutes
  3. customseparating cartridge
  4. customthe organic layer evaporated
  5. customto afford crude product
  6. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  7. additionFractions containing the desired compound
  8. customwere evaporated to dryness

出典と根拠

ORDレコード
ord-61f36f0d1f624046971bd8a35172d7a9
出典データセット
uspto-grants-2011_08
特許番号
US08003649B2

反応ノート

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