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)-morpholine-2,4-dicarboxylic acid 4-tert-butyl ester

HRID 2176240Notes

Reaction equation

HRID 2176240 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]([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.[C:35]([O:39][C:40]([N:42]1[CH2:47][CH2:46][O:45][C:44]([CH:51]=[CH2:52])([C:48]([OH:50])=[O:49])[CH2:43]1)=[O:41])([CH3:38])([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]>[C:35]([O:39][C:40]([N:42]1[CH2:47][CH2:46][O:45][C:44](/[CH:51]=[CH:52]/[C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]4[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]([CH3:30])[CH3:31])[CH3:25])[NH:18]4)=[O:16])[CH3:13])=[N:9]3)=[CH:4][CH:3]=2)([C:48]([OH:50])=[O:49])[CH2:43]1)=[O:41])([CH3:38])([CH3:37])[CH3:36]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 867060782-Vinyl-morpholine-2,4-dicarboxylic acid 4-tert-butyl esterHCID 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]-amide

Product 1

HCID 867060792-((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)-morpholine-2,4-dicarboxylic acid 4-tert-butyl ester

Reagents, catalysts & solvents 2

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

Conditions

Temperature
50 °C

Procedure

A solution 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 (95 mg, 0.178 mmol), 2-vinyl-morpholine-2,4-dicarboxylic acid 4-tert-butyl ester (45.7 mg, 0.178 mmol), tri(o-tolyl)phosphine (11 mg, 0.036 mmol) and triethylamine (0.08 mL, 0.534 mmol) in 1,4-dioxane (5 mL) was degassed by bubbling nitrogen through for 5 minutes then warmed to 50° C. and treated with tris(dibenzylideneacetone)dipalladium(0) (16.3 mg, 0.018 mmol). After stirring at 100° C. for 50 minutes 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) 711.3 [M+H], Tr=2.14 min.

Workup

  1. customby bubbling nitrogen through for 5 minutes
  2. temperaturewas cooled to room temperature
  3. filtrationfiltered through a pad of Celite, which
  4. washwas rinsed with ethyl acetate
  5. customThe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-62eccad6deb649ebaefbdf303051a7b3
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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