Diisopropylethylamine → 2-((2-(5-((5S,7S)-7-((6-cyano-1H-benzo[d]imidazol-1-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-3-yl)pyrazin-2-yl)propan-2-yl)oxy)ethyl dimethylphosphinate

HRID 715548ノート

反応式

HRID 715548 の反応式
[OH:1][CH2:2][CH2:3][O:4][C:5]([C:8]1[N:9]=[CH:10][C:11]([N:14]2[CH2:18][C@@:17]3([CH2:23][CH2:22][CH2:21][C@@:20]([CH2:25][N:26]4[C:30]5[CH:31]=[C:32]([C:35]#[N:36])[CH:33]=[CH:34][C:29]=5[N:28]=[CH:27]4)([CH3:24])[CH2:19]3)[O:16][C:15]2=[O:37])=[N:12][CH:13]=1)([CH3:7])[CH3:6].CCN(C(C)C)C(C)C.[CH3:47][P:48](Cl)([CH3:50])=[O:49]>ClCCl>[CH3:47][P:48]([CH3:50])(=[O:49])[O:1][CH2:2][CH2:3][O:4][C:5]([C:8]1[CH:13]=[N:12][C:11]([N:14]2[CH2:18][C@@:17]3([CH2:23][CH2:22][CH2:21][C@@:20]([CH2:25][N:26]4[C:30]5[CH:31]=[C:32]([C:35]#[N:36])[CH:33]=[CH:34][C:29]=5[N:28]=[CH:27]4)([CH3:24])[CH2:19]3)[O:16][C:15]2=[O:37])=[CH:10][N:9]=1)([CH3:7])[CH3:6]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 517954Dimethylphosphinic chlorideHCID 712275921-(((5S,7S)-3-(5-(2-(2-hydroxyethoxy)propan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

生成物 1

HCID 712276992-((2-(5-((5S,7S)-7-((6-cyano-1H-benzo[d]imidazol-1-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-3-yl)pyrazin-2-yl)propan-2-yl)oxy)ethyl dimethylphosphinate収率 8.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 1-(((5S,7S)-3-(5-(2-(2-hydroxyethoxy)propan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (60 mg, 0.119 mmol) in dichloromethane (DCM) (1127 μl) was added DIEA (62.3 μl, 0.357 mmol) and dimethylphosphinic chloride (40.1 mg, 0.357 mmol) at RT. The mixture was stirred for 2 hours, concentrated and reconstituted in DMSO/MeOH and filtered. The solution was purified by reverse phase HPLC (Waters Sunfire 30×150 mm Acetonitrile: Water TFA 30-70%, 50 mL/min, 15 min.). The product was free based with PL-HCO3 resin SPE to yield 2-((2-(5-((5S,7S)-7-((6-cyano-1H-benzo[d]imidazol-1-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-3-yl)pyrazin-2-yl)propan-2-yl)oxy)ethyl dimethylphosphinate as a white solid (5.8 mg, 8%). 1H NMR (400 MHz, DMSO-d6) δ 9.24 (d, J=1.51 Hz, 1H), 8.60 (d, J=1.26 Hz, 1H), 8.48 (s, 1H), 8.38 (s, 1H), 7.83 (d, J=8.53 Hz, 1H), 4.12-4.21 (m, 2H), 3.94-4.03 (m, 2H), 3.88 (dd, J=23.09, 10.04 Hz, 2H), 3.42 (t, J=4.77 Hz, 2H), 2.00 (d, J=13.30 Hz, 1H), 1.88 (d, J=14.05 Hz, 1H), 1.59-1.78 (m, 3H), 1.30-1.56 (m, 15H), 1.07 (s, 3H). MS (m/z) 581.3 (M+H+).

後処理

  1. concentrationconcentrated
  2. filtrationfiltered
  3. customThe solution was purified by reverse phase HPLC (Waters Sunfire 30×150 mm Acetonitrile: Water TFA 30-70%, 50 mL/min, 15 min.)

出典と根拠

ORDレコード
ord-349321e13bc2463a9f3f690dcd33d624
出典データセット
uspto-grants-2015_11
特許番号
US09187464B2

反応ノート

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