Ethyl cyanoacetate → HCID 71585106, compound

HRID 1430518Notes

Reaction equation

HRID 1430518 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:15]3[C:16]([Br:32])=[CH:17][C:18]([F:31])=[C:19]([NH:21][C:22]([NH:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[O:23])[CH:20]=3)[C:8](=[O:14])[N:9]2[CH2:12][CH3:13])=[CH:4][N:3]=1.[C:33]([CH2:35][C:36](OCC)=[O:37])#[N:34]>CN1C(=O)CCC1>[Br:32][C:16]1[CH:17]=[C:18]([F:31])[C:19]([NH:21][C:22]([NH:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:23])=[CH:20][C:15]=1[C:7]1[C:8](=[O:14])[N:9]([CH2:12][CH3:13])[C:10]2[C:5]([CH:6]=1)=[CH:4][N:3]=[C:2]([NH:1][C:36](=[O:37])[CH2:35][C:33]#[N:34])[CH:11]=2

Participants

4

Reactant 2

HCID 7764Ethyl cyanoacetateHCID 71585077HCID 71585077, compound

Product 1

HCID 71585106HCID 71585106, compoundYield 8.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
125 °C

Procedure

A suspension of Example 57 (135 mg, 0.272 mmol) in ethyl cyanoacetate (2.307 g, 20.40 mmol) was heated at 105° C. for 4.5 h, then at 125° C. for 2 days. The mixture was treated with NMP (0.3 mL), heated at 125° C. for 5 h, then cooled to RT and purified via silica gel chromatography (EtOAc/Hex). The material was re-purified via silica gel chromatography (THF/Hex), dissolved in 4:1 MeCN/H2O, frozen and lyophilized. The material was treated with MTBE, the resulting solid collected via filtration and dried to afford N-(3-(2-bromo-4-fluoro-5-(3-phenylureido)phenyl)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)-2-cyanoacetamide (13 mg, 8.5% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.17 (s, 1H), 9.10 (s, 1H), 8.74 (m, 2H), 8.23 (d, J=8.5 Hz, 1H), 8.17 (s, 1H), 7.98 (s, 1H), 7.70 (d, J=10.7 Hz, 1H), 7.41 (d, J=8.1 Hz, 2H), 7.26 (t, J=7.8 Hz, 2H), 6.97 (t, J=7.4 Hz, 1H), 4.22 (q, J=7.2 Hz, 2H), 4.05 (s, 2H), 1.26 (t, J=6.8 Hz, 3H); MS (ESI) m/z: 565.1 [M+H]+.

Workup

  1. temperaturecooled to RT
  2. custompurified via silica gel chromatography (EtOAc/Hex)
  3. customThe material was re-purified via silica gel chromatography (THF/Hex)
  4. dissolutiondissolved in 4:1 MeCN/H2O
  5. temperaturefrozen
  6. additionThe material was treated with MTBE
  7. filtrationthe resulting solid collected via filtration
  8. customdried

Sources & evidence

ORD record
ord-368aa888c57441ac9b42de6eff2f38d7
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

Loading…