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3-Aminopyridine → (2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid pyridin-3-ylamide

HRID 1807312
ノート
印刷プレビュー

反応式

HRID 1807312 の反応式
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([F:38])=[C:11]([C@@H:15]2[C@:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[F:29])([C:20]#[N:21])[C@H:18]([CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[NH:17][C@H:16]2[C:35]([OH:37])=O)[CH:12]=[CH:13][CH:14]=1.CCN(C(C)C)C(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[NH2:63][C:64]1[CH:65]=[N:66][CH:67]=[CH:68][CH:69]=1>C(Cl)Cl>[N:66]1[CH:67]=[CH:68][CH:69]=[C:64]([NH:63][C:35]([C@H:16]2[C@H:15]([C:11]3[CH:12]=[CH:13][CH:14]=[C:9]([Cl:8])[C:10]=3[F:38])[C@:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=3[F:29])([C:20]#[N:21])[C@H:18]([CH2:30][C:31]([CH3:32])([CH3:34])[CH3:33])[NH:17]2)=[O:37])[CH:65]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 100093-AminopyridineHCID 73910Diphenylphosphinic chlorideHCID 81531DiisopropylethylamineHCID 86642695CID 86642695

生成物 1

HCID 53358570(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid pyridin-3-ylamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

In a 25 mL round-bottomed flask, (2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acid compound with 2,2,2-trifluoroacetic acid (1:1) (200 mg, 344 μmol, Eq: 1.00), was combined with CH2Cl2 (3 ml) to give a colorless solution. DIPEA (240 μl, 1.38 mmol, Eq: 4) and diphenylphosphinic chloride (244 mg, 1.03 mmol, Eq: 3) were added and the reaction was stirred at RT for 20 minutes. 3-Amino-pyridine (38.9 mg, 413 μmol, Eq: 1.2) was added and the reaction mixture was stirred at RT overnight. The crude reaction mixture was concentrated in vacuum. The crude material was purified by flash chromatography (silica gel, 40 g, 2% to 5% MeOH in DCM) to give a white solid as the product. 185 mg. MS (ES+) m/z Calcd: [(M+H)+]: 543. found: 543.

後処理

  1. customto give a colorless solution
  2. stirringthe reaction mixture was stirred at RT overnight
  3. customThe crude reaction mixture
  4. concentrationwas concentrated in vacuum
  5. customThe crude material was purified by flash chromatography (silica gel, 40 g, 2% to 5% MeOH in DCM)
  6. customto give a white solid as the product

出典と根拠

ORDレコード
ord-d892c5e2af0c418fa8ccbbf706a08aba
出典データセット
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08354444B2

反応ノート

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