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Sodium Carbonate → 3-(aminocarbonyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-N-(2,4,6-trimethyl-3-pyridinyl)-1-piperazineacetamide trihydrochloride

HRID 1494655
ノート
印刷プレビュー

反応式

HRID 1494655 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH:14]2[C:19]([NH2:21])=[O:20])=[CH:4][CH:3]=1.[ClH:29].[Cl:30][CH2:31][C:32]([NH:34][C:35]1[C:36]([CH3:43])=[N:37][C:38]([CH3:42])=[CH:39][C:40]=1[CH3:41])=[O:33].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[ClH:30].[ClH:29].[ClH:30].[NH2:21][C:19]([CH:14]1[N:13]([CH2:12][CH2:11][CH2:10][CH2:9][CH:8]([C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:18][CH2:17][N:16]([CH2:31][C:32]([NH:34][C:35]2[C:36]([CH3:43])=[N:37][C:38]([CH3:42])=[CH:39][C:40]=2[CH3:41])=[O:33])[CH2:15]1)=[O:20]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 10340Sodium CarbonateHCID 150877291-[5,5-Bis(4-fluorophenyl)pentyl]-2-piperazinecarboxamideHCID 198284682-chloro-N-(2,4,6-trimethyl-3-pyridinyl)acetamide monohydrochloride

生成物 1

HCID 867448813-(aminocarbonyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-N-(2,4,6-trimethyl-3-pyridinyl)-1-piperazineacetamide trihydrochloride収率 61.2%

試薬・触媒・溶媒 1

HCID 6228
Dimethylformamide
溶媒

反応条件

温度
70 °C

実験手順

A mixture of 6.1 parts of 1-[5,5-bis(4-fluorophenyl)pentyl]-2-piperazinecarboxamide, 4.3 parts of 2-chloro-N-(2,4,6-trimethyl-3-pyridinyl)acetamide monohydrochloride, 3.7 parts of sodium carbonate and 90 parts of N,N-dimethylformamide was stirred for 15 hours at 70° C. The reaction mixture was filtered, washed with N,N-dimethylformamide and the filtrate was evaporated in vacuo. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (92.5:7.5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was further purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the hydrochloride salt in 2-propanone and 2-propanol. The salt was filtered off, washed twice with 2-propanone and once with 2,2'-oxybispropane and dried overnight at 100°-110° C., yielding 6.58 parts (61.2%) of 3 -(aminocarbonyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-N-(2,4,6-trimethyl-3-pyridinyl)-1-piperazineacetamide trihydrochloride, hemihydrate; mp. 224.7° C. (compound 115).

後処理

  1. filtrationThe reaction mixture was filtered
  2. washwashed with N,N-dimethylformamide
  3. customthe filtrate was evaporated in vacuo
  4. customThe residue was purified by column chromatography over silica gel using
  5. additiona mixture of trichloromethane and methanol (92.5:7.5 by volume) as eluent
  6. customThe pure fractions were collected
  7. customthe eluent was evaporated
  8. customThe residue was further purified by column chromatography over silica gel using
  9. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  10. customThe pure fractions were collected
  11. customthe eluent was evaporated
  12. filtrationThe salt was filtered off
  13. washwashed twice with 2-propanone and once with 2,2'-oxybispropane
  14. customdried overnight at 100°-110° C.

出典と根拠

ORDレコード
ord-f874b8c716e64c1c80d106ad1ba3a556
出典データセット
uspto-grants-1991_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US05026853

反応ノート

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