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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
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HRID 588741 반응식
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]
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참가 물질

5

반응물 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

생성물 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

시약·촉매·용매 1

HCID 887Methanol용매2회

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온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-5cf315517cc34388a17812c67283c646
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09227972B2

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