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 1778016Notes

Reaction equation

HRID 1778016 reaction equation
[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]

Participants

6

Reactant 2

HCID 57469773Phenyl (5-cyanopyridin-2-yl)carbamate2×HCID 1180368332-(dimethoxymethyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]azepine2×

Product 1

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

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-298e1136ed694a768473c791ca4b26e4
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

Loading…