Diisopropylethylamine → (R)-benzyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate

HRID 539723

反応式

HRID 539723 の反応式
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[C:15]([F:38])=[C:16]([CH:35]=[CH:36][CH:37]=1)[CH2:17][N:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[C@H:20]([CH3:34])[CH2:19]1.CCN(C(C)C)C(C)C.[NH2:48][C:49]1[CH:54]=[CH:53][N:52]=[C:51]([CH3:55])[CH:50]=1>C1COCC1.CCOC(C)=O>[F:38][C:15]1[C:14]([NH:13][C:5]([NH:48][C:49]2[CH:54]=[CH:53][N:52]=[C:51]([CH3:55])[CH:50]=2)=[O:11])=[CH:37][CH:36]=[CH:35][C:16]=1[CH2:17][N:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[C@H:20]([CH3:34])[CH2:19]1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 7286704-Amino-2-methylpyridineHCID 58919233(R)-benzyl 4-(3-amino-2-fluorobenzyl)-2-methylpiperazine-1-carboxylate

生成物 1

HCID 58919234(R)-benzyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate収率 27%

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 (150 mg, 0.50 mmol, 0.35 equiv) in THF (15 mL) was slowly added via cannula a solution of (R)-benzyl 4-(3-amino-2-fluorobenzyl)-2-methylpiperazine-1-carboxylate (500 mg, 1.4 mmol, 1.0 equiv) and DIPEA (485 μL, 18.5 mmol, 2.0 equiv) in THF (15 mL) over approximately 15 minutes. The solution was stirred for an additional 20 min at 0° C., and 4-amino-2-methylpyridine was then added. After stirring at room temperature overnight, 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 (R)-benzyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)-2-methylpiperazine-1-carboxylate (180 mg, 27%). LCMS m/z (APCI)=492.3 (M+H).

後処理

  1. stirringAfter stirring at room temperature overnight
  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-cac495ea6a9a4abf83e48b825f74c5bc
出典データセット
uspto-grants-2014_10
特許番号
US08871768B2

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