Potassium Phosphate, Tribasic → HCID 178502475、化合物

HRID 1751616ノート

反応式

HRID 1751616 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:30](=[CH:31][CH:32]=1)[C:8]1[NH:9][C:10]([C@@H:12]3[C@H:17]4[CH2:18][C@H:14]([CH2:15][CH2:16]4)[N:13]3[C:19](=[O:29])[C@@H:20]([NH:24][C:25](=[O:28])[O:26][CH3:27])[CH:21]([CH3:23])[CH3:22])=[N:11][C:7]=1[CH:6]=[CH:5]2.CC1(C)C(C)(C)OB([C:41]2[CH:42]=[C:43]3[C:63](=[CH:64][CH:65]=2)[C:47]2[NH:48][C:49]([C@@H:51]4[CH2:55][CH2:54][CH2:53][N:52]4[C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])=[N:50][C:46]=2[CH:45]=[CH:44]3)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.C(OCC)(=O)C>[CH3:27][O:26][C:25]([NH:24][C@@H:20]([CH:21]([CH3:23])[CH3:22])[C:19]([N:13]1[C@H:12]([C:10]2[NH:9][C:8]3[C:30]4[C:4]([CH:5]=[CH:6][C:7]=3[N:11]=2)=[CH:3][C:2]([C:41]2[CH:42]=[C:43]3[C:63](=[CH:64][CH:65]=2)[C:47]2[NH:48][C:49]([C@@H:51]5[CH2:55][CH2:54][CH2:53][N:52]5[C:56]([O:58][C:59]([CH3:61])([CH3:62])[CH3:60])=[O:57])=[N:50][C:46]=2[CH:45]=[CH:44]3)=[CH:32][CH:31]=4)[C@H:17]2[CH2:18][C@@H:14]1[CH2:15][CH2:16]2)=[O:29])=[O:28]

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 178451892HCID 178451892、化合物HCID 178502473HCID 178502473、化合物

生成物 1

HCID 178502475HCID 178502475、化合物収率 67.1%

試薬・触媒・溶媒 2

HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Methyl (S)-1-((1S,3S,4R)-3-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-3-methyl-1-oxobutan-2-ylcarbamate (0.300 g, 0.601 mmol), (S)-tert-butyl 2-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (0.334 g, 0.721 mmol), and aqueous potassium phosphate (2M, 0.901 mL, 1.802 mmol) were suspended in 1,2-dimethoxyethane (3.00 mL) and sparged with argon gas for 30 minutes. Palladium tetrakis triphenylphosphine (0.069 g, 0.060 mmol) was added and the reaction mixture was capped and placed in a preheated 80° C. oil bath. The solution was heated for 18 hours and subsequently stirred at room temperature for two days. Upon completion, the reaction was diluted with ethyl acetate and washed with brine. The concentrated organic layer was purified by normal phase chromatography (40-100% ethyl acetate (10% MeOH) in hexanes) to give (S)-tert-butyl 2-(2′-((1S,3S,4R)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[2.2.1]heptan-3-yl)-1H,1′H-7,7′-binaphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (0.305 g, 67%). LCMS-ESI+: calc'd for C44H49N7O5: 755.38 (M+); Found: 756.8 (M+H+).

後処理

  1. customsparged with argon gas for 30 minutes
  2. customthe reaction mixture was capped
  3. customplaced in a preheated 80° C.
  4. temperatureThe solution was heated for 18 hours
  5. washwashed with brine
  6. customThe concentrated organic layer was purified by normal phase chromatography (40-100% ethyl acetate (10% MeOH) in hexanes)

出典と根拠

ORDレコード
ord-780bd4befaa6449d91d4c469039767e5
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

読み込み中…