Triethylamine → N1-Methyl-5-(2-((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamide

HRID 2376922노트

반응식

HRID 2376922 반응식
[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[C:20]([C:21]#[N:22])=[CH:19][N:18]=[C:17]([NH2:23])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4].C(N(CC)CC)C.Cl[C:32](OC1C=CC=CC=1)=[O:33].[N:41]1([CH:46]2[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]2)[CH2:45][CH2:44][CH2:43][CH2:42]1>O1CCCC1.CN(C)C=O.O>[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[C:20]([C:21]#[N:22])=[CH:19][N:18]=[C:17]([NH:23][C:32]([N:49]4[CH2:50][CH2:51][CH:46]([N:41]5[CH2:45][CH2:44][CH2:43][CH2:42]5)[CH2:47][CH2:48]4)=[O:33])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4]

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 787034-(1-Pyrrolidinyl)piperidineHCID 21949164N1-methyl-5-(2-amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamide

생성물 1

HCID 21949191N1-Methyl-5-(2-((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamide수율 25.1%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

실험 절차

N1-Methyl-5-(2-amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamide (15 mg, 0.049 mmol) synthesized in Example 215 was suspended in tetrahydrofuran (0.5 ml) at room temperature; triethylamine (17 μl, 0.122 mmol) and phenyl chloroformate (14 μl, 0.072 mmol) was added thereto while stirring; and the reaction mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, this was subjected to extraction with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. N,N-Dimethylformamide (0.5 ml) and 4-(1-pyrrolidinyl)piperidine (28 mg, 0.18 mmol) was added to a portion of the residue (14 mg); and the reaction mixture was stirred at room temperature overnight. The reaction mixture was partitioned between ethyl acetate and water; and the organic layer was dried over anhydrous sodium sulfate. This was concentrated under reduced pressure; and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol). The resultant was washed with a solvent mixture (ether:hexane=1:1); and the solid was filtered off to yield the title compound as crystals (6 mg).

후처리

  1. stirringand the reaction mixture was stirred at room temperature for 2 hours
  2. extractionthis was subjected to extraction with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. stirringand the reaction mixture was stirred at room temperature overnight
  7. customThe reaction mixture was partitioned between ethyl acetate and water
  8. dry with materialand the organic layer was dried over anhydrous sodium sulfate
  9. concentrationThis was concentrated under reduced pressure
  10. customand the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol)
  11. washThe resultant was washed with a solvent mixture (ether:hexane=1:1)
  12. filtrationand the solid was filtered off

출처 및 근거

ORD 기록
ord-35c21255a3384c1d8dc0b2220948e896
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07468380B2

반응 노트

불러오는 중…