N,1-dimethylpyrrolidin-3-amine → HCID 178423457、化合物

HRID 77109

反応式

HRID 77109 の反応式
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=O)[CH2:11][CH2:10]2)=[CH:5][C:4]=1[C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:20]=2[N:19]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:52][NH:53][CH:54]1[CH2:58][CH2:57][N:56]([CH3:59])[CH2:55]1>>[CH3:52][N:53]([CH:54]1[CH2:58][CH2:57][N:56]([CH3:59])[CH2:55]1)[C:15]([CH:12]1[CH2:11][CH2:10][N:9]([C:6]2[CH:7]=[CH:8][C:3]([Cl:2])=[C:4]([C:18]3[NH:22][C:21]4[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:20]=4[N:19]=3)[CH:5]=2)[CH2:14][CH2:13]1)=[O:17]

参加物

4

反応物 3

HCID 2758520N,1-dimethylpyrrolidin-3-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178423459HCID 178423459、化合物

生成物 1

HCID 178423457HCID 178423457、化合物収率 37%

反応条件

温度
35 °C

実験手順

Method Q—Step a To a mixture of 1-[4-chloro-3-(5-methyl-1H-benzoimidazol-2-yl)-phenyl]-piperidine-4-carboxylic acid hydrochloride (obtained as described in general method 3,4, step e) (0.01 g, 0.25 mmol) in dcm (2 mL), HATU (0.10 g, 0.26 mmol), TEA (0.07 mL, 0.53 mmol) and methyl-(1-methyl-pyrrolidin-3-yl)-amine (0.03 g, 0.31 mmol) were added. The reaction mixture was heated at 35° C. overnight, cooled to room temperature, washed with ammonium chloride solution (2 mL), filtered through a phase separator and organic phase was filtered by SCX column (eluent: first dcm:MeOH/1:1 then NH3 in MeOH (2N)). This work up was done using the Zinsser Speedy (version 6.1.3). The crude was then purified by flash chromatography (eluent: gradient from EtOAc to EtOAc:NH3 in MeOH (2N)/10:1) to obtain 0.04 g of the title compound (37%). 1H-NMR (400 MHz, CD3OD): δ 1.76-1.93 (5H, m), 2.08-2.23 (2H, m), 2.36-2.48 (6H, m), 2.51-3.09 (9H, m), 3.83-3.86 (2H, m), 5.13-5.20 (1H, m), 7.09-7.13 (2H, m), 7.38-7.40 (3H, m), 7.51 (1H, bs); m/z 466 (M+H)+, retention time (method b)=2.30 (10 min run)

後処理

  1. additionwere added
  2. temperaturecooled to room temperature
  3. washwashed with ammonium chloride solution (2 mL)
  4. filtrationfiltered through a phase separator and organic phase
  5. filtrationwas filtered by SCX column (eluent
  6. customThe crude was then purified by flash chromatography (eluent: gradient from EtOAc to EtOAc:NH3 in MeOH (2N)/10:1)

出典と根拠

ORDレコード
ord-d383427c471749b58667f644ea369eb4
出典データセット
uspto-grants-2014_09
特許番号
US08835648B2

関連ノート

読み込み中…