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 2176326Notes

Reaction equation

HRID 2176326 reaction equation
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

Participants

7

Reactant 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

Product 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 acidYield 100%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-343839660f774e22bc6b43315a1b24ce
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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