Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (S)-tert-butyl 4-((4-((3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl) carbamoyl)pyridin-2-yl)amino)piperidine-1-carboxylate

HRID 2202084ノート

反応式

HRID 2202084 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:16]=[C:17]([CH:21]=[CH:22][N:23]=2)[C:18](O)=[O:19])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:48][CH2:49][C@H:50]([OH:62])[CH2:51][N:52]1[CH2:61][CH2:60][C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[CH2:53]1>C(Cl)Cl>[CH2:53]1[C:54]2[C:59](=[CH:58][CH:57]=[CH:56][CH:55]=2)[CH2:60][CH2:61][N:52]1[CH2:51][C@@H:50]([OH:62])[CH2:49][NH:48][C:18]([C:17]1[CH:21]=[CH:22][N:23]=[C:15]([NH:14][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]2)[CH:16]=1)=[O:19]

参加物

5

反応物 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 25312355(S)-1-Amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-olHCID 902380262-((1-(Tert-butoxycarbonyl)piperidin-4-yl)amino)isonicotinic acid

生成物 1

HCID 90241001(S)-tert-butyl 4-((4-((3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl) carbamoyl)pyridin-2-yl)amino)piperidine-1-carboxylate収率 53.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
20 °C

実験手順

To a solution of 2-((1-(tert-butoxycarbonyl)piperidin-4-yl)amino)isonicotinic acid (150 g, 0.47 mol) in DCM (1500 mL) was added HATU (178 g, 0.47 mol) and TEA (47 g, 0.47 mol) at 20° C., then the mixture was stirred at the temperature for 2 h. (S)-1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (113 g, 0.55 mol) was added to the solution, and the mixture was stirred at 20° C. for another 16 h, at which time TLC showed the completion of the reaction. The mixture washed with water (200 mL) and the combined organic phases were dried and concentrated. The residue was purified by flash chromatography (EtOAc˜DCM:MeOH=10:1) to give the title compound as yellowish oil. Four batches were run in parallel and produced a combined product weight of 510 g, yield: 53.2%. LCMS (m/z): 510.2 [M+H]+.

後処理

  1. additionwas added to the solution
  2. customthe completion of the reaction
  3. washThe mixture washed with water (200 mL)
  4. customthe combined organic phases were dried
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (EtOAc˜DCM:MeOH=10:1)

出典と根拠

ORDレコード
ord-cab27e9d3a2f4581a3817320ba2fa109
出典データセット
uspto-grants-2016_06
特許番号
US09365519B2

反応ノート

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