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

HRID 539723

반응식

HRID 539723 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-cac495ea6a9a4abf83e48b825f74c5bc
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871768B2

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