Hydrochloric Acid → HCID 178485822、化合物

HRID 333496

反応式

HRID 333496 の反応式
[CH3:1][O:2][C:3](=[O:55])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][C:30]([NH:33][C:34]([C:36]4[CH:37]=[N:38][C:39]([N:42]5[CH2:47][C@H:46]([CH3:48])[NH:45][CH2:44][C@H:43]5[CH3:49])=[CH:40][CH:41]=4)=[O:35])=[CH:29][C:28]=3[O:50][C:51]([F:54])([F:53])[F:52])=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].C(N(CC)C(C)C)(C)C.[CH3:65][NH:66][C:67](Cl)=[O:68].Cl>C(Cl)Cl.CC(N(C)C)=O.O>[CH3:1][O:2][C:3](=[O:55])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][C:30]([NH:33][C:34]([C:36]4[CH:37]=[N:38][C:39]([N:42]5[CH2:47][C@H:46]([CH3:48])[N:45]([C:67](=[O:68])[NH:66][CH3:65])[CH2:44][C@H:43]5[CH3:49])=[CH:40][CH:41]=4)=[O:35])=[CH:29][C:28]=3[O:50][C:51]([F:54])([F:52])[F:53])=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:7])[CH3:8]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 80931Methylcarbamoyl chloride2 回HCID 81531DiisopropylethylamineHCID 178502383((S)-1-{(S)-2-[4-(4'-{[6-((2R,5S)-2,5-Dimethyl-piperazin-1-yl)-pyridine-3-carbonyl]-amino}-2'-trifluoromethoxy-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

生成物 1

HCID 178485822HCID 178485822、化合物

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 31374Dimethylacetamide溶媒2 回

実験手順

To a solution of ((S)-1-{(S)-2-[4-(4′-{[6-((2R,5S)-2,5-dimethyl-piperazin-1-yl)-pyridine-3-carbonyl]-amino}-2′-trifluoromethoxy-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (62.8 g, 74.1 mmol; Preparation 3) and N,N-diisopropylethylamine (20.1 mL, 115.2 mmol) in DCM (750 mL) was slowly added 1 M methylaminoformyl chloride in DMA (68.4 mL) over 10 min at 10-15° C. After 50 min, 1 M methylaminoformyl chloride in DMA (3.6 mL) was added and the reaction mixture was stirred overnight. To the reaction mixture was added water (750 mL) and 1 N HCl (40 mL). The organic layer was washed with water, dried over Na2SO4, and evaporated. Methanol (300 mL) and 2 N LiOH (10 mL) were added to the crude product and the reaction mixture was stirred for 30 min. Water (110 mL) was added slowly to the reaction mixture. Seeds of crystalline title product were added after 50 mL of water. The reaction mixture was stirred for 2 days and then methanol (60 mL) and water (24 mL) were added. After 30 min, the mixture was filtered. The solid was washed with 2:1 methanol:water (120 mL), and dried under vacuum at 35° C. overnight to provide the title compound (54 g).

後処理

  1. customover 10 min
  2. customat 10-15° C
  3. washThe organic layer was washed with water
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. additionMethanol (300 mL) and 2 N LiOH (10 mL) were added to the crude product
  7. stirringthe reaction mixture was stirred for 30 min
  8. additionWater (110 mL) was added slowly to the reaction mixture
  9. additionSeeds of crystalline title product were added after 50 mL of water
  10. stirringThe reaction mixture was stirred for 2 days
  11. additionmethanol (60 mL) and water (24 mL) were added
  12. waitAfter 30 min
  13. filtrationthe mixture was filtered
  14. washThe solid was washed with 2:1 methanol
  15. dry with materialwater (120 mL), and dried under vacuum at 35° C. overnight

出典と根拠

ORDレコード
ord-8032d1dff32a452cb61789e14c9045ac
出典データセット
uspto-grants-2014_11
特許番号
US08883135B2

関連ノート

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