Water → Alvelestat

HRID 1517471Notes

Reaction equation

HRID 1517471 reaction equation
[CH3:1][C:2]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[C:6](=[O:18])[C:5]([C:19]([OH:21])=O)=[CH:4][C:3]=1[C:22]1[N:26]([CH3:27])[N:25]=[CH:24][CH:23]=1.Cl.[CH3:29][S:30]([C:33]1[CH:34]=[CH:35][C:36]([CH2:39][NH2:40])=[N:37][CH:38]=1)(=[O:32])=[O:31].O>C(#N)C>[CH3:1][C:2]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:16])([F:15])[F:17])[CH:9]=2)[C:6](=[O:18])[C:5]([C:19]([NH:40][CH2:39][C:36]2[CH:35]=[CH:34][C:33]([S:30]([CH3:29])(=[O:32])=[O:31])=[CH:38][N:37]=2)=[O:21])=[CH:4][C:3]=1[C:22]1[N:26]([CH3:27])[N:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 962WaterHCID 594558756-Methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acidHCID 66725223[5-(Methanesulfonyl)pyridin-2-yl]methanaminium chloride

Product 1

HCID 46861623AlvelestatYield 96%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
50 °C

Procedure

6-Methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acid (52.0 kg, 1 mol eq, limiting reagent) and acetonitrile (208 L, 4 rel vol,) were charged. The reaction mixture was heated to 50° C. 1,1′-s carbonyldiimidazole as a solution in acetonitrile (208 L, 4 rel vol) is charged to the reaction until the reaction is complete as judged by HPLC. C-(5-(Methanesulfonyl)pyridine-2-yl)methylamine monohydrochloride (33.8 kg, 1.1 mol eq) was charged and the reaction maintained at 50° C. until the reaction was deemed complete as judged by HPLC. Water (780 L, 15 rel vol) was charged. The reaction mixture was stirred, cooled and further stirred. The solid was collected by filtration and washed twice with water (2×104 L, 2×2 rel vol) and dried to constant weight to yield the title compound (96.0 kg, 176.0 mol, 96%); 1H NMR (d6-DMSO): δ 1.83 (s, 3H); 3.29 (s, 3H); 3.72 (s, 3H); 4.73 (d, 2H, J 5.8 Hz); 6.33 (d, 1H, J=1.9 Hz); 7.53 (d, 1H, J=1.9 Hz); 7.57 (d, 1H, J 8.3 Hz); 7.81-7.88 (m, 2H); 7.92-7.94 (m, 1H); 8.03 (s, 1H); 8.21 (s, 1H); 8.27 (dd, 1H, J 2.3, 7.9 Hz); 8.99 (d, 1H, J=2.3 Hz); 10.06 (t, 1H, J 6.0 Hz); LCMS: m/z 546.3 (MH+).

Workup

  1. additionwere charged
  2. temperaturethe reaction maintained at 50° C. until the reaction
  3. temperaturecooled
  4. stirringfurther stirred
  5. filtrationThe solid was collected by filtration
  6. washwashed twice with water (2×104 L, 2×2 rel vol)
  7. customdried to constant weight

Sources & evidence

ORD record
ord-3df95681d663401dbcd622c7b4d1f491
Source dataset
uspto-grants-2012_07
Patent number
US08232296B2

Reaction notes

Loading…