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 2176240ノート

反応式

HRID 2176240 の反応式
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]

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
50 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-62eccad6deb649ebaefbdf303051a7b3
出典データセット
uspto-grants-2015_06
特許番号
US09062092B2

反応ノート

読み込み中…