Triethylamine → 6-((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)-[1,4]dioxepane-6-carboxylic acid

HRID 2176276ノート

反応式

HRID 2176276 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.[CH:35]([C:37]1([C:44]([OH:46])=[O:45])[CH2:43][O:42][CH2:41][CH2:40][O:39][CH2:38]1)=[CH2:36].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:36]=[CH:35]/[C:37]4([C:44]([OH:46])=[O:45])[CH2:43][O:42][CH2:41][CH2:40][O:39][CH2:38]4)=[CH:3][CH:4]=3)[N:9]=2)[CH3:13])=[O:16])[NH:18]1)=[O:34])=[O:33]

参加物

7

反応物 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 867061206-Vinyl-[1,4]dioxepane-6-carboxylic acid

生成物 1

HCID 867061216-((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)-[1,4]dioxepane-6-carboxylic acid

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 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 (68 mg, 0.128 mmol), 6-vinyl-[1,4]dioxepane-6-carboxylic acid (22 mg, 0.128 mmol), triethylamine (39 mg, 54 μL, 0.384 mmol) and tri(o-tolyl)phosphine (8 mg, 0.026 mmol) in 1,4-dioxane (2 mL) was deoxygenated by bubbling nitrogen through for 5 minutes and then warmed to 50° C. under nitrogen with stirring. Tris(dibenzylideneacetone)dipalladium(0) (12 mg, 0.013 mmol) was added and the mixture was refluxed for 40 minutes and then allowed to cool. The suspension was filtered and the filtrate was evaporated to give crude title compound which was used directly in the next stage. LCMS (m/z) 626.2 [M+H], Tr=1.67 min.

後処理

  1. customwas deoxygenated
  2. customby bubbling nitrogen through for 5 minutes
  3. temperaturethe mixture was refluxed for 40 minutes
  4. temperatureto cool
  5. filtrationThe suspension was filtered
  6. customthe filtrate was evaporated

出典と根拠

ORDレコード
ord-8160dd6bbdb243e2b23279664ef6744d
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…