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Hydrochloric Acid → (6S)-3-(1,1-Difluoro-2-(((3S,5S,6R)-6-methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl)amino)ethyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

HRID 588741
ノート
印刷プレビュー

反応式

HRID 588741 の反応式
Cl.[F:2][C:3]([C:26]1[CH:27]=[C:28]2[CH2:51][C@@:33]3([C:41]4[C:36](=[N:37][CH:38]=[CH:39][CH:40]=4)[N:35](COCC[Si](C)(C)C)[C:34]3=[O:50])[CH2:32][C:29]2=[N:30][CH:31]=1)([F:25])[CH2:4][NH:5][C@H:6]1[CH2:11][C@@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C@@H:9]([CH3:18])[N:8]([CH2:19][C:20]([F:23])([F:22])[F:21])[C:7]1=[O:24].[OH-].[NH4+]>CO>[F:2][C:3]([C:26]1[CH:27]=[C:28]2[CH2:51][C@@:33]3([C:41]4[C:36](=[N:37][CH:38]=[CH:39][CH:40]=4)[NH:35][C:34]3=[O:50])[CH2:32][C:29]2=[N:30][CH:31]=1)([F:25])[CH2:4][NH:5][C@H:6]1[CH2:11][C@@H:10]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C@@H:9]([CH3:18])[N:8]([CH2:19][C:20]([F:23])([F:21])[F:22])[C:7]1=[O:24]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 131734441(6S)-3-(1,1-Difluoro-2-(((3S,5S,6R)-6-methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl)amino)ethyl)-1'((2-(trimethylsilyl)ethoxy)methyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

生成物 1

HCID 72199094(6S)-3-(1,1-Difluoro-2-(((3S,5S,6R)-6-methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl)amino)ethyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

反応条件

温度
0 °C

実験手順

HCl gas was bubbled into a solution of (6S)-3-(1,1-difluoro-2-(((3S,5S,6R)-6-methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl)amino)ethyl)-1′-((2-(trimethylsilyl)ethoxy)methyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (0.012 g, 0.017 mmol) in MeOH (3 mL) cooled to 0° C. until saturated. The resulting mixture was stirred at 0° C. for 1 h and then concentrated to dryness in vacuo. To a solution of this crude mixture in MeOH (5 mL) was added ammonium hydroxide (0.047 mL, 0.335 mmol), and the reaction was stirred at ambient temperature for 30 min. The reaction was concentrated to dryness in vacuo. The crude product was purified by reverse-phase HPLC, eluting with 10% acetonitrile in water (0.1% TFA used as a modifier) initially, grading to 80% acetonitrile in water, to give the title compound. MS: m/z=586.2 (M+1). 1H NMR (500 MHz, CDCl3) δ 8.77 (s, 1H), 8.04 (d, 1H, J=7.0 Hz), 8.00 (s, 1H), 7.90 (bs, 1H), 7.61 (d, 1H, J=7.0 Hz), 7.40-7.29 (m, 3H), 7.26-7.10 (m, 3H), 4.87-4.81 (m, 1H), 4.07 (dd, 1H, J=11.4, 6.8 Hz), 3.98 (s, 2H), 3.90-3.75 (m, 3H), 3.73 (d, 1H, J=17.6 Hz), 3.57-3.48 (m, 2H), 3.38 (d, 1H, J=17.1 Hz), 3.35-3.27 (m, 1H), 2.63 (dt, 1H, J=12.5 Hz), 2.49-2.47 (m, 1H), 0.98 (d, 3H, J=6.5 Hz).

後処理

  1. concentrationconcentrated to dryness in vacuo
  2. stirringthe reaction was stirred at ambient temperature for 30 min
  3. concentrationThe reaction was concentrated to dryness in vacuo
  4. customThe crude product was purified by reverse-phase HPLC
  5. washeluting with 10% acetonitrile in water (0.1% TFA

出典と根拠

ORDレコード
ord-5cf315517cc34388a17812c67283c646
出典データセット
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09227972B2

反応ノート

読み込み中…

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