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

HRID 2093443노트

반응식

HRID 2093443 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-260b8aeeb79442ad84648682953c03c7
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445495B2

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