Glycine ethyl ester, hydrochloride → {5-[2-(4-Acetylamino-phenylsulfanyl)-5-methyl-phenylamino]-[1,8]naphthyridin-2-ylamino}-acetic acid ethyl ester

HRID 2197740Notes

Reaction equation

HRID 2197740 reaction equation
Cl[C:2]1[N:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:14]=3[S:20][C:21]3[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:30])[CH3:29])=[CH:23][CH:22]=3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.Cl.[CH2:32]([O:34][C:35](=[O:38])[CH2:36][NH2:37])[CH3:33]>CCO>[CH2:32]([O:34][C:35](=[O:38])[CH2:36][NH:37][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[N:9][CH:8]=[CH:7][C:6]=2[NH:12][C:13]2[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:14]=2[S:20][C:21]2[CH:22]=[CH:23][C:24]([NH:27][C:28](=[O:30])[CH3:29])=[CH:25][CH:26]=2)[N:11]=1)[CH3:33]

Participants

4

Reactant 2

HCID 2723640Glycine ethyl ester, hydrochlorideHCID 86615485N-{4-[2-(7-Chloro-[1,8]naphthyridin-4-ylamino)-4-methyl-phenylsulfanyl]-phenyl}-acetamide

Product 1

HCID 68461945{5-[2-(4-Acetylamino-phenylsulfanyl)-5-methyl-phenylamino]-[1,8]naphthyridin-2-ylamino}-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The product from Example 24a (47 mg, 0.10 mmol) was reacted with the glycine ethyl ester hydrochloride (84 mg, 0.10 mmol) in 2 mL of EtOH in a sealed tube at 150° C. for 1 h. Cooled to room temperature and concentrated. Adjusted to pH 7 with 1M HCl and extracted with EtOAc, dried over Na2SO4, filtered and concentrated under vacuum giving the crude title compound which was purified by HPLC with TFA providing the product as a trifluoroacetic acid solid (12 mg, 19%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.22 (t, J=6.99 Hz, 3H) 2.04 (s, 3H) 2.33 (s, 3H) 4.15 (q, J=7.23 Hz, 2H) 4.27 (d, J=6.25 Hz, 2H) 6.08 (d, J=6.99 Hz, 1H) 7.04 (d, J=5.52 Hz, 1H) 7.07 (d, J=6.62 Hz, 1H) 7.19-7.30 (m, 4H) 7.57 (d, J=8.46 Hz, 2H) 8.04 (t, J=6.62 Hz, 1H) 8.53 (d, J=9.19 Hz, 1H) 8.72 (t, J=5.88 Hz, 1H) 10.08 (s, 1H) 10.43 (s, 1H) 13.43 (d, J=5.88 Hz, 1H); MS (ESI+) m/z 502 (M+H−TFA)+.

Workup

  1. concentrationconcentrated
  2. extractionextracted with EtOAc
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-90d5b20b8bc44676906794db17a8c863
Source dataset
uspto-grants-2012_12
Patent number
US08338605B2

Reaction notes

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