Diisopropylethylamine → Tert-butyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)piperazine-1-carboxylate

HRID 539715

反応式

HRID 539715 の反応式
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[C:15]([F:34])=[C:16]([CH:31]=[CH:32][CH:33]=1)[CH2:17][N:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1.CCN(C(C)C)C(C)C.[NH2:44][C:45]1[CH:50]=[CH:49][N:48]=[C:47]([CH3:51])[CH:46]=1>C1COCC1.CCOC(C)=O>[F:34][C:15]1[C:14]([NH:13][C:5]([NH:44][C:45]2[CH:50]=[CH:49][N:48]=[C:47]([CH3:51])[CH:46]=2)=[O:11])=[CH:33][CH:32]=[CH:31][C:16]=1[CH2:17][N:18]1[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:22][CH2:23]1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 7286704-Amino-2-methylpyridineHCID 58919232Tert-butyl 4-(3-amino-2-fluorobenzyl)piperazine-1-carboxylate

生成物 1

HCID 58919226Tert-butyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)piperazine-1-carboxylate収率 43%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

To a 0° C. solution of triphosgene (959 mg, 3.24 mmol, 0.35 equiv) in THF (45 mL) was slowly added via cannula a solution of tert-butyl 4-(3-amino-2-fluorobenzyl)piperazine-1-carboxylate (2.86 g, 9.25 mmol, 1.0 equiv) and DIPEA (3.2 mL, 18.5 mmol, 2.0 equiv) in THF (25 mL) over approximately 20 minutes. The solution was stirred for an additional 15 min at 0° C., and 4-amino-2-methylpyridine was then added. After stirring at room temperature for 72 h, the reaction was diluted with EtOAc, washed with aq. satd. NaHCO3 and brine, dried over sodium sulfate, filtered and concentrated in vacuo. Purification by reverse phase preparative HPLC provided tert-butyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)piperazine-1-carboxylate (1.77 g, 43%). LCMS m/z (APCI)=444.3 (M+H).

後処理

  1. stirringAfter stirring at room temperature for 72 h
  2. washwashed with aq. satd
  3. dry with materialNaHCO3 and brine, dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-d2596ea1680648daab9a84ecb290a8dc
出典データセット
uspto-grants-2014_10
特許番号
US08871768B2

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