N,N-二异丙基乙胺 → 3-Fluoro-4'-{(1r)-1-[({1-[(3,3,3-trifluoropropanoyl)amino]cyclopropyl}carbonyl)-amino]ethyl}-1,1'-biphenyl-2-carboxylic acid

HRID 10069

反应方程式

HRID 10069 反应方程式
[F:1][C:2]([F:8])([F:7])[CH2:3][C:4](O)=[O:5].Cl.C(N=C=NCCCN(C)C)C.ON1C2N=CC=CC=2N=N1.[NH2:31][C:32]1([C:35]([NH:37][C@@H:38]([C:40]2[CH:45]=[CH:44][C:43]([C:46]3[C:47]([C:53]([OH:55])=[O:54])=[C:48]([F:52])[CH:49]=[CH:50][CH:51]=3)=[CH:42][CH:41]=2)[CH3:39])=[O:36])[CH2:34][CH2:33]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[F:52][C:48]1[CH:49]=[CH:50][CH:51]=[C:46]([C:43]2[CH:42]=[CH:41][C:40]([C@H:38]([NH:37][C:35]([C:32]3([NH:31][C:4](=[O:5])[CH2:3][C:2]([F:8])([F:7])[F:1])[CH2:34][CH2:33]3)=[O:36])[CH3:39])=[CH:45][CH:44]=2)[C:47]=1[C:53]([OH:55])=[O:54]

参与物

7

反应物 5

HCID 81531N,N-二异丙基乙胺HCID 181649N-羟基-7-氮杂苯并三氮唑HCID 27239391-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐HCID 27779723,3,3-三氟丙酸HCID 695631874'-((1R)-1-{[(1-aminocyclopropyl)carbonyl]amino}ethyl)-3-fluoro-1,1'-biphenyl-2-carboxylic acid

产物 1

HCID 695640683-Fluoro-4'-{(1r)-1-[({1-[(3,3,3-trifluoropropanoyl)amino]cyclopropyl}carbonyl)-amino]ethyl}-1,1'-biphenyl-2-carboxylic acid

试剂、催化剂与溶剂 1

HCID 6344二氯甲烷溶剂2 次

实验过程

To a solution of trifluoropropionic acid (128 mg, 1.0 mmol) in DCM (1 mL), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (229 mg, 1.2 mmol) and 1-hydroxy-7-azabenzotriazole (136 mg, 1.0 mmol) were added. The resulting solution was stirred at room temperature for 20 minutes, then 4′-((1R)-1-{[(1-aminocyclopropyl)carbonyl]amino}ethyl)-3-fluoro-1,1′-biphenyl-2-carboxylic acid (171 mg, 0.5 mmol) in 1 mL DCM was added, followed by N,N-diisopropylethylamine until pH=10 was achieved. The reaction mixture was stirred at ambient temperature under N2 for 2 hours, concentrated under vacuum and then partitioned between water and ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluted with 40% MeOH in CHCl3. Collection and concentration of appropriate fractions provided 3-fluoro-4′-{(1R)-1-[({1-[(3,3,3-trifluoropropanoyl)amino]cyclopropyl}carbonyl)-amino]ethyl}-1,1′-biphenyl-2-carboxylic acid as a white powder.

后处理

  1. stirringThe reaction mixture was stirred at ambient temperature under N2 for 2 hours
  2. concentrationconcentrated under vacuum
  3. custompartitioned between water and ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. washeluted with 40% MeOH in CHCl3
  10. customCollection and concentration of appropriate fractions

来源与证据

ORD记录
ord-dd2ed1d732e747bca66ca981bc217465
来源数据集
uspto-grants-2006_08
专利号
US07091380B2

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