Acetic Acid → 2,4,6-Trifluoro-n-[6-(1-cyclopropylmethyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide dihydrochloride salt

HRID 30222

反応式

HRID 30222 の反応式
[F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[O:14])[N:8]=1)=[O:5].[CH:27]1([CH:30]=O)[CH2:29][CH2:28]1.C(O)(=O)C.[Na].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Cl:50]CCl>CO>[ClH:50].[ClH:50].[F:26][C:21]1[CH:22]=[C:23]([F:25])[CH:24]=[C:2]([F:1])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([CH:15]2[CH2:16][CH2:17][N:18]([CH2:30][CH:27]3[CH2:29][CH2:28]3)[CH2:19][CH2:20]2)=[O:14])[N:8]=1)=[O:5]

参加物

7

反応物 5

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 123114CyclopropanecarboxaldehydeHCID 179803372,4,6-trifluoro-N-(6-(piperidine-4-carbonyl)pyridin-2-yl)benzamideHCID 131725371CID 131725371

生成物 1

HCID 179803042,4,6-Trifluoro-n-[6-(1-cyclopropylmethyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide dihydrochloride salt収率 77%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

Combine 2,4,6-trifluoro-N-[6-(piperidin-4-ylcarbonyl)pyridin-2-yl]benzamide (0.05 g, 0.138 mmol), cyclopropylmethanal (0.10 g, 1.38 mmol) and dichloromethane (5 mL), and stir at ambient temperature. After 15 minutes, add glacial acetic acid (0.02 mL, 0.35 mmol) followed by sodium-triacetoxyborohydride (0.038 g, 0.18 mmol) with stirring. After 3 hrs., dilute the reaction mixture with methanol (5 mL) and load on an SCX column (10 g). Wash the column with methanol, elute with 2M ammonia/methanol, and concentrate the eluent. Purify the residue by flash chromatography, eluting with 10% ammonia/methanol in dichloromethane, to obtain the free base of the title compound (0.045 g, 77%). Dissolve the free base in dichloromethane (5 mL), treat with 1M hydrogen chloride in diethylether (0.25 mL), and concentrate the mixture to obtain the dihydrochloride salt. M.p.=140° C.; HRMS: Obs. m/z 418.1743; Calc. m/z 418.1742; 1H NMR (CDCl3): 11.51 (bs, 1H), 10.34 (bs, 1H), 8.38 (m, 1H), 8.11 (m, 1H), 7.78(d, 1H), 7.42 (m, 2H), 3.79 (m, 1H), 3.64 (m, 2H), 2.98 (m, 4H), 2.17 (m, 2H), 1.99 (m, 2H), 1.13 (m, 1H), 0.65 (m, 2H), 0.39 (m, 2H).

後処理

  1. waitAfter 3 hrs
  2. washWash the column with methanol
  3. washelute with 2M ammonia/methanol
  4. concentrationconcentrate the eluent
  5. customPurify the residue by flash chromatography
  6. washeluting with 10% ammonia/methanol in dichloromethane

出典と根拠

ORDレコード
ord-a78185fd7779447ba9b8e89babe8eb2c
出典データセット
uspto-grants-2008_09
特許番号
US07423050B2

関連ノート

読み込み中…