P-Toluenesulfonamide → HCID 178427614, compound

HRID 1470320Notes

Reaction equation

HRID 1470320 reaction equation
[OH:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[C:4]([C:11]2[N:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1.OC1C(C(OC)=O)=CN=C(C2N=NC=CC=2)N=1.[OH-].[Na+].C(OC1C(C(OCC)=O)=CN=C(N2C=CC=N2)N=1)C1C=CC=CC=1.C(OC1C(C(O)=O)=CN=C(N2C=CC=N2)N=1)C1C=CC=CC=1.[CH3:82][C:83]1[CH:84]=[CH:85][C:86]([S:89]([NH2:92])(=[O:91])=[O:90])=[CH:87][CH:88]=1.C(N(CC)CC)C>S(Cl)(Cl)=O.CN(C1C=CN=CC=1)C>[OH:1][C:2]1[C:7]([C:8]([NH:92][S:89]([C:86]2[CH:87]=[CH:88][C:83]([CH3:82])=[CH:84][CH:85]=2)(=[O:90])=[O:91])=[O:10])=[CH:6][N:5]=[C:4]([C:11]2[N:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=1

Participants

10

Reactant 7

HCID 6269P-ToluenesulfonamideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 674594834-(benzyloxy)-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxylic acidHCID 67460482Ethyl 4-(benzyloxy)-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxylateHCID 178498780HCID 178498780, compoundHCID 178524753HCID 178524753, compound

Product 1

HCID 178427614HCID 178427614, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 24386Thionyl ChlorideSolvent

Procedure

4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxylic acid, 13-b, (350 mg, 1.6 mmol, which was prepared from compound 1-e via sodium hydroxide hydrolysis in a similar manner as the conversion of 3-b to 3-c) in thionyl chloride (10 ml) was heated at reflux for 4 h. The mixture was concentrated under vacuum and the residue was co-evaporated with dichloromethane twice. The remaining oil was dissolved in dichloromethane (10 ml). p-toluenesulfonamide (329 mg, 1.93 mmol), triethylamine (486 mg, 4.82 mmol) and DMAP (390 mg, 3.2 mmol) were added to the solution at room temperature. The mixture was subsequently stirred at room temperature overnight. The mixture was then concentrated under vacuum and the residue was diluted with water (10 ml). The solid crashed out and then filtered out of the solution. The solids were then recrystallization in methanol/ethyl acetate to afford compound 13-1 (300 mg, 50%). 1H NMR (DMSO-d6, 300 MHz): δ 12.92 (br, 1H), 9.51 (s, 1H), 8.53 (s, 2H), 8.00 (m, 3H), 7.46 (s, 2H), 2.41 (s, 3H). (M+H)+=372.1.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 h
  3. concentrationThe mixture was concentrated under vacuum
  4. dissolutionThe remaining oil was dissolved in dichloromethane (10 ml)
  5. concentrationThe mixture was then concentrated under vacuum
  6. additionthe residue was diluted with water (10 ml)
  7. filtrationfiltered out of the solution
  8. customrecrystallization in methanol/ethyl acetate

Sources & evidence

ORD record
ord-3f270b6372414e1ea95493bcd6e4578a
Source dataset
uspto-grants-2015_04
Patent number
US09006433B2

Reaction notes

Loading…