2,4,6-Trifluorobenzoyl chloride → HCID 69351067、化合物

HRID 970747ノート

反応式

HRID 970747 の反応式
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([F:12])[C:3]=1[C:4]([Cl:6])=[O:5].[CH3:13][N:14]([CH3:28])[CH:15]1[CH2:20][CH2:19][C:18]([C:21]2[N:26]=[C:25]([NH2:27])[CH:24]=[CH:23][CH:22]=2)=[CH:17][CH2:16]1>N1C=CC=CC=1.Cl>[ClH:6].[ClH:6].[CH3:13][N:14]([CH3:28])[CH:15]1[CH2:20][CH2:19][C:18]([C:21]2[N:26]=[C:25]([NH:27][C:4](=[O:5])[C:3]3[C:2]([F:1])=[CH:10][C:9]([F:11])=[CH:8][C:7]=3[F:12])[CH:24]=[CH:23][CH:22]=2)=[CH:17][CH2:16]1

参加物

5

反応物 2

HCID 1448952,4,6-Trifluorobenzoyl chloride2 回HCID 588523656-(4-Dimethylamino-cyclohex-1-enyl)-pyridin-2-ylamine

生成物 1

HCID 69351067HCID 69351067、化合物収率 49%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 1049Pyridine溶媒

反応条件

温度
55 °C

実験手順

Add 2,4,6-trifluorobenzoyl chloride (117 mg, 0.60 mmol) to a solution of 6-(4-dimethylamino-cyclohex-1-enyl)-pyridin-2-ylamine, isomer 1 (preparation 10, 100 mg, 0.46 mmol) in pyridine (6 mL) and heat at 55° C. overnight. Re-add another portion of 2,4,6-trifluorobenzoyl chloride (50 mg, 0.26 mmol) and heat at 65° C. for 4 hr. Remove volatiles under reduced pressure, dissolve the residue in 1N HCl, extract twice with ethyl ether. Adjust aqueous layer to pH>11 with 5N NaOH. Extract the aqueous layer there times with DCM. Combine organic layers, dry over sodium sulfate, filter and concentrate to give a residue. Purify the residue by chromatography (silica gel, 5% 2M NH3/MeOH in DCM) to provide the free amine of the title compound as a colorless oil (84 mg, 49%): MS (ion spray): m/z=376.2 (M+H)+; 1H NMR (CDCl3): δ 8.91 (s, br, 1H), 8.20 (d, 1H), 7.73 (t, 1H), 7.14 (d, 1H), 6.71 (m, 2H), 6.61 (m, 1H), 2.65 (m, 1H), 2.44 (m, 3H), 2.35 (s, 6H), 2.12 (m, 2H), 1.53 (m, 1H). Using a salt formation method similar to that in example 1 provides the di-hydrochloride salt. Di-hydrochloride salt: Anal. cal'd for C20H20F3N3O.2HCl: C, 53.58; H, 4.95; N, 9.37. Found: C, 53.42; H, 4.91; N, 9.23.

後処理

  1. extractionextract twice with ethyl ether
  2. extractionExtract the aqueous layer there times with DCM
  3. dry with materialCombine organic layers, dry over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. customto give a residue
  7. customPurify the residue by chromatography (silica gel, 5% 2M NH3/MeOH in DCM)

出典と根拠

ORDレコード
ord-a40fa0fc19924724b828155c59d974c5
出典データセット
uspto-grants-2007_12
特許番号
US07312236B2

反応ノート

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