Triethylamine → 2-((E)-2-{2-[(R)-1-({(S)-1-[(S)-2-((S)-2-Hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carbonyl}-amino)-ethyl]-quinolin-7-yl}-vinyl)-5,5-dimethyl[1,4]dioxane-2-carboxylic acid

HRID 2176322노트

반응식

HRID 2176322 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]([OH:32])[CH:29]([CH3:31])[CH3:30])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[CH3:35][C:36]1([CH3:47])[CH2:41][O:40][C:39]([CH:45]=[CH2:46])([C:42]([OH:44])=[O:43])[CH2:38][O:37]1.C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>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]>[OH:32][C@@H:28]([CH:29]([CH3:31])[CH3:30])[C:27]([NH:26][C@@H:24]([CH3:25])[C:23]([N:19]1[CH2:20][CH2:21][CH2:22][C@@H:17]([C:15]([NH:14][C@@H:12]([C:8]2[CH:7]=[CH:6][C:5]3[C:10](=[CH:11][C:2](/[CH:46]=[CH:45]/[C:39]4([C:42]([OH:44])=[O:43])[CH2:38][O:37][C:36]([CH3:35])([CH3:47])[CH2:41][O:40]4)=[CH:3][CH:4]=3)[N:9]=2)[CH3:13])=[O:16])[NH:18]1)=[O:34])=[O:33]

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 86706080(S)-1-[(S)-2-((S)-2-hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amideHCID 867061705,5-Dimethyl-2-vinyl-[1,4]dioxane-2-carboxylic acid

생성물 1

HCID 867061712-((E)-2-{2-[(R)-1-({(S)-1-[(S)-2-((S)-2-Hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carbonyl}-amino)-ethyl]-quinolin-7-yl}-vinyl)-5,5-dimethyl[1,4]dioxane-2-carboxylic acid수율 100%

시약·촉매·용매 2

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

반응 조건

온도
50 °C

실험 절차

A mixture of (S)-1-[(S)-2-((S)-2-hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amide (198 mg, 0.371 mmol), 5,5-dimethyl-2-vinyl-[1,4]dioxane-2-carboxylic acid (69 mg, 0.371 mmol), triethylamine (112 mg, 155 μL, 1.11 mmol) and tri(o-tolyl)phosphine (23 mg, 0.074 mmol) in 1,4-dioxane (7.5 mL) was degassed with nitrogen for 5 min and then warmed to 50° C. under nitrogen with stirring. Tris(dibenzylideneacetone)dipalladium(0) (34 mg, 0.037 mmol) was added and the mixture was heated to 80° C. for 40 min and then allowed to cool to room temperature. The suspension was filtered and evaporated to give crude title compound (0.371 mmol) which was used directly in the next stage. LCMS (m/z) 640.3 [M+H], Tr=1.94 min.

후처리

  1. customwas degassed with nitrogen for 5 min
  2. temperaturethe mixture was heated to 80° C. for 40 min
  3. temperatureto cool to room temperature
  4. filtrationThe suspension was filtered
  5. customevaporated

출처 및 근거

ORD 기록
ord-6b62bb843ee74e1fa518cd17c5f05d38
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09062092B2

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