Triethylamine → HCID 86706102, compound

HRID 2176261Notes

Reaction equation

HRID 2176261 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:35])[C@@H:24]([NH:26][C:27](=[O:34])[C@H:28]([CH:30]4[CH2:33][CH2:32][CH2:31]4)[OH:29])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[CH3:36][C:37]([CH3:43])([CH:41]=[CH2:42])[C:38]([OH:40])=[O:39].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].[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[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:42]=[CH:41]/[C:37]([CH3:43])([CH3:36])[C:38]([OH:40])=[O:39])=[CH:3][CH:4]=4)[N:9]=3)[CH3:13])=[O:16])[NH:18]2)=[O:35])=[O:34])[CH2:33][CH2:32][CH2:31]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphine2×HCID 1391223-Butenoic acid, 2,2-dimethyl-HCID 86706103HCID 86706103, compound

Product 1

HCID 86706102HCID 86706102, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A solution of (S)-1-[(S)-2-((S)-2-cyclobutyl-2-hydroxy-acetylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amide (427.5 mg, 0.782 mmol), 2,2-dimethyl-but-3-enoic acid (89.3 mg, 0.782 mmol), tri(o-tolyl)phosphine (47.6 mg, 0.156 mmol) and triethylamine (0.33 mL, 2.346 mmol) in 1,4-dioxane (10 mL) was degassed by bubbling nitrogen through for 5 minutes then warmed to 50° C. and treated with tris(dibenzylideneacetone)dipalladium(0) (71.6 mg, 0.078 mmol). After stirring at 100° C. for 1.5 h, tris(dibenzylideneacetone) dipalladium(0) (71.6 mg, 0.078 mmol) and tri(o-tolyl)phosphine (47.6 mg, 0.156 mmol) were added. After stirring for 40 minutes at 100° C., the reaction was cooled to room temperature, filtered through a pad of Celite, which was rinsed with ethyl acetate. The volatiles were removed in vacuo to provide crude title compound as an orange foam that was used without further purification. LCMS (m/z) 580.2 [M+H], Tr=2.01 min.

Workup

  1. customby bubbling nitrogen through for 5 minutes
  2. stirringAfter stirring for 40 minutes at 100° C.
  3. temperaturethe reaction was cooled to room temperature
  4. filtrationfiltered through a pad of Celite, which
  5. washwas rinsed with ethyl acetate
  6. customThe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-3a3ca54c7ed64da89f3297267a20ede0
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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