Pyridine → (S)-4-[2-(3-Fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-2-methoxycarbonylmethyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 1963070ノート

反応式

HRID 1963070 の反応式
[F:1][C:2]1[C:3]([CH3:24])=[C:4]([CH:21]=[CH:22][CH:23]=1)[CH2:5][C:6]1[C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:8]2[N:13]([CH:14]=1)[CH:12]=[CH:11][CH:10]=[CH:9]2.N1C=CC=CC=1.[C:31](Cl)(Cl)=[O:32].C1(C)C=CC=CC=1.[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][NH:52][CH2:51][C@@H:50]1[CH2:55][C:56]([O:58][CH3:59])=[O:57])=[O:48])([CH3:45])([CH3:44])[CH3:43].C(N(CC)CC)C>C(Cl)Cl>[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][N:52]([C:31]([C:14]2[N:13]3[C:8]([CH:9]=[CH:10][CH:11]=[CH:12]3)=[C:7]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:6]=2[CH2:5][C:4]2[CH:21]=[CH:22][CH:23]=[C:2]([F:1])[C:3]=2[CH3:24])=[O:32])[CH2:51][C@@H:50]1[CH2:55][C:56]([O:58][CH3:59])=[O:57])=[O:48])([CH3:45])([CH3:44])[CH3:43]

参加物

8

反応物 6

HCID 1049PyridineHCID 1140TolueneHCID 6371PhosgeneHCID 8471TriethylamineHCID 29414379tert-Butyl (2S)-2-(2-methoxy-2-oxoethyl)piperazine-1-carboxylateHCID 677730242-(3-Fluoro-2-methyl-benzyl)-1-phenyl-indolizine

生成物 1

HCID 67772153(S)-4-[2-(3-Fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-2-methoxycarbonylmethyl-piperazine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

To a solution of the compound of example 1, step 3 (1.32 g, 4.19 mmol) in 20 ml of DCM at 0° C. were added pyridine (0.34 ml, 4.19 mmol) and then a 20% solution of phosgene in toluene (2.20 ml, 4.19 mmol). The mixture was stirred at room temperature for 1.5 h and then added dropwise to an ice-cooled (0° C.) solution of the compound of step 3 (1.189 g, 4.60 mmol) and triethylamine (0.58 ml, 4.60 mmol) in 32 ml of DCM. The mixture was stirred at room temperature overnight, then diluted with 30 ml of DCM and washed twice with 1 N hydrochloric acid, twice with a saturated sodium hydrogencarbonate solution and twice with brine. The organic phase was dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica gel (cyclohexane/EA, 80:20, then 70:30) to give 1.44 g of the title compound as a pale yellow-green powder.

後処理

  1. stirringThe mixture was stirred at room temperature overnight
  2. washwashed twice with 1 N hydrochloric acid, twice with a saturated sodium hydrogencarbonate solution and twice with brine
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (cyclohexane/EA, 80:20

出典と根拠

ORDレコード
ord-8abc84f792ad4486bad162b0d90f1284
出典データセット
uspto-grants-2013_04
特許番号
US08415336B2

反応ノート

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