Phenyl (5-cyanopyridin-2-yl)carbamate → N-(5-cyanopyridin-2-yl)-2-(dimethoxymethyl)-7,8-dihydro-5H-pyrido[2,3-b]azepine-9(6H)-carboxamide

HRID 1778016노트

반응식

HRID 1778016 반응식
[CH3:1][O:2][CH:3]([O:15][CH3:16])[C:4]1[CH:5]=[CH:6][C:7]2[CH2:13][CH2:12][CH2:11][CH2:10][NH:9][C:8]=2[N:14]=1.C1([O:23][C:24](=O)[NH:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][N:27]=2)C=CC=CC=1>CN(C1C=CN=CC=1)C.C1COCC1.C([O-])(O)=O.[Na+]>[C:32]([C:29]1[CH:30]=[CH:31][C:26]([NH:25][C:24]([N:9]2[CH2:10][CH2:11][CH2:12][CH2:13][C:7]3[CH:6]=[CH:5][C:4]([CH:3]([O:2][CH3:1])[O:15][CH3:16])=[N:14][C:8]2=3)=[O:23])=[N:27][CH:28]=1)#[N:33]

참가 물질

6

반응물 2

HCID 57469773Phenyl (5-cyanopyridin-2-yl)carbamate2회HCID 1180368332-(dimethoxymethyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]azepine2회

생성물 1

HCID 118037151N-(5-cyanopyridin-2-yl)-2-(dimethoxymethyl)-7,8-dihydro-5H-pyrido[2,3-b]azepine-9(6H)-carboxamide

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 8028Tetrahydrofuran용매HCID 516892Sodium Bicarbonate용매

실험 절차

A mixture of 2-(dimethoxymethyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]azepine (intermediate 237, 35 mg, 0.154 mmol), phenyl(5-cyanopyridin-2-yl)carbamate (intermediate 240, 122 mg, 0.509 mmol) and DMAP (28.3 mg, 0.231 mmol) in THF (1.7 ml) was heated at reflux for 23 h. The reaction mixture was diluted with sat. aq. NaHCO3 and extracted with DCM (3×). The combined organic layers were dried over Na2SO4 and evaporated. The crude material was applied to a 40 g RediSep® silica column and purified by normal phase chromatography, eluting with 99:1 DCM/MeOH. Product-containing fractions were combined and evaporated. The residue was triturated with Et2O and the solid removed by filtration. The filtrate was concentrated and the residue triturated with MeOH to give the title compound as a white solid. (UPLC-MS 6) tR 1.06; ESI-MS 368.1 [M+H]+.

후처리

  1. temperaturewas heated
  2. temperatureat reflux for 23 h
  3. extractionextracted with DCM (3×)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. customevaporated
  6. custompurified by normal phase chromatography
  7. washeluting with 99:1 DCM/MeOH
  8. customevaporated
  9. customThe residue was triturated with Et2O
  10. customthe solid removed by filtration
  11. concentrationThe filtrate was concentrated
  12. customthe residue triturated with MeOH

출처 및 근거

ORD 기록
ord-298e1136ed694a768473c791ca4b26e4
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09266883B2

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