Triethylamine → 1-((E)-2-{2-[(R)-1-({(S)-1-[(S)-2-((S)-2-Cyclopropyl-2-hydroxy-acetylamino)-propionyl]-hexahydro-pyridazine-3-carbonyl}-amino)-ethyl]-quinolin-7-yl}-vinyl)-3-triisopropylsilanyloxy-cyclopentanecarboxylic acid

HRID 2176326노트

반응식

HRID 2176326 반응식
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:34])[C@@H:24]([NH:26][C:27](=[O:33])[C@H:28]([CH:30]4[CH2:32][CH2:31]4)[OH:29])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[CH:35]([Si:38]([CH:53]([CH3:55])[CH3:54])([CH:50]([CH3:52])[CH3:51])[O:39][CH:40]1[CH2:44][CH2:43][C:42]([CH:48]=[CH2:49])([C:45]([OH:47])=[O:46])[CH2:41]1)([CH3:37])[CH3:36].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:30]1([C@H:28]([OH:29])[C:27]([NH:26][C@@H:24]([CH3:25])[C:23]([N:19]2[CH2:20][CH2:21][CH2:22][C@@H:17]([C:15]([NH:14][C@@H:12]([C:8]3[CH:7]=[CH:6][C:5]4[C:10](=[CH:11][C:2](/[CH:49]=[CH:48]/[C:42]5([C:45]([OH:47])=[O:46])[CH2:43][CH2:44][CH:40]([O:39][Si:38]([CH:50]([CH3:52])[CH3:51])([CH:53]([CH3:55])[CH3:54])[CH:35]([CH3:36])[CH3:37])[CH2:41]5)=[CH:3][CH:4]=4)[N:9]=3)[CH3:13])=[O:16])[NH:18]2)=[O:34])=[O:33])[CH2:32][CH2:31]1

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 86706134(S)-1-[(S)-2-((S)-2-cyclopropyl-2-hydroxy-acetylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amideHCID 867061743-Triisopropylsilanyloxy-1-vinyl-cyclopentanecarboxylic acid

생성물 1

HCID 867061751-((E)-2-{2-[(R)-1-({(S)-1-[(S)-2-((S)-2-Cyclopropyl-2-hydroxy-acetylamino)-propionyl]-hexahydro-pyridazine-3-carbonyl}-amino)-ethyl]-quinolin-7-yl}-vinyl)-3-triisopropylsilanyloxy-cyclopentanecarboxylic acid수율 100%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

A solution of (S)-1-[(S)-2-((S)-2-cyclopropyl-2-hydroxy-acetylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amide (795.0 mg, 1.493 mmol), 3-triisopropylsilanyloxy-1-vinyl-cyclopentanecarboxylic acid (466.6 mg, 1.493 mmol), tri(o-tolyl)phosphine (91.0 mg, 0.299 mmol) and triethylamine (0.63 mL, 4.479 mmol) in 1,4-dioxane (20 mL) was deoxygenated by bubbling through nitrogen for 5 min. The reaction mixture was then treated with tris(dibenzylideneacetone)dipalladium(0) (136.7 mg, 0.149 mmol). After stirring at 100° C. for 40 min, the reaction was cooled to room temperature and filtered through Celite. The solid was rinsed with ethyl acetate and the volatiles were removed in vacuo to provide the crude title compound (1.493 mmol) as an orange foam. LCMS (m/z) 764.4 [M−H], Tr=3.53 min.

후처리

  1. customby bubbling through nitrogen for 5 min
  2. temperaturethe reaction was cooled to room temperature
  3. filtrationfiltered through Celite
  4. washThe solid was rinsed with ethyl acetate
  5. customthe volatiles were removed in vacuo

출처 및 근거

ORD 기록
ord-343839660f774e22bc6b43315a1b24ce
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09062092B2

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