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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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1-(3-Aminoazetidin-1-yl)ethan-1-one → (s)-6-((1-acetylazetidin-3-yl)amino)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide

HRID 2202089
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HRID 2202089 반응식
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][CH2:11][C@H:12]([OH:24])[CH2:13][N:14]2[CH2:23][CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:9])[CH:3]=1.[NH2:25][CH:26]1[CH2:29][N:28]([C:30](=[O:32])[CH3:31])[CH2:27]1>CC(O)C>[C:30]([N:28]1[CH2:29][CH:26]([NH:25][C:2]2[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][CH2:11][C@H:12]([OH:24])[CH2:13][N:14]3[CH2:23][CH2:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH2:15]3)=[O:9])[CH:3]=2)[CH2:27]1)(=[O:32])[CH3:31]
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참가 물질

4

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HCID 545278501-(3-Aminoazetidin-1-yl)ethan-1-oneHCID 90241529(S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide

생성물 1

HCID 90245426(s)-6-((1-acetylazetidin-3-yl)amino)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide수율 112.7%

시약·촉매·용매 1

HCID 3776Isopropanol용매

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온도
60 °C

실험 절차

To a solution of (S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl) pyrimi dine-4-carboxamide (240 g, 0.69 mol) in i-PrOH (2.5 L) was added 1-(3-amino azetidin-1-yl)ethanone (120 g) and TEA (100 g). After addition, the solution was heated at 60° C. for 16 h, at which time LCMS showed completion of the reaction. The mixture was concentrated and the residue was purified by flash chromatography to give the crude product. Four batches were run in parallel and produced a combined crude product weight of 420 g, 90% purity. This crude was further purified on preparative HPLC to give the title compound (330 g, >98% purity, free base form). 1H NMR (400 MHz, MeOD-d4) 8.27 (s, 1H), 7.12-6.98 (m, 5H), 4.71 (s, 1H), 4.54 (m, 1H), 4.32 (m, 1H), 4.06 (m, 2H), 3.88 (m, 1H), 3.70 (s, 2H), 3.53-3.50 (m, 2H), 2.91-2.83 (m, 4H), 2.65 (m, 2H), 1.88 (s, 3H); LCMS (m/z): 425.2 [M+H]+

후처리

  1. additionAfter addition
  2. customcompletion of the reaction
  3. concentrationThe mixture was concentrated
  4. customthe residue was purified by flash chromatography
  5. customto give the crude product
  6. customproduced a combined crude product weight of 420 g, 90% purity
  7. customThis crude was further purified on preparative HPLC

출처 및 근거

ORD 기록
ord-33ca380081604282ae20d86af730e2da
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09365519B2

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