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 880347ノート

反応式

HRID 880347 の反応式
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]

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
60 °C

実験手順

To a solution of (S)-6-chloro-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-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]+

後処理

  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

出典と根拠

ORDレコード
ord-6d51fb436b744c7a829fc1325a1313b3
出典データセット
uspto-grants-2015_03
特許番号
US08993555B2

反応ノート

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