Triethylamine → ethyl 4-((4-chlorophenyl)(1-methyl-6-oxo-1,6-dihydropyridin-3-ylamino)methyl)-1-(4-methoxybenzyl)-5-methyl-1H-pyrazole-3-carboxylate

HRID 873794Notes

Reaction equation

HRID 873794 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[C:10]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[N:11][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:13]=2[CH3:14])=[CH:4][CH:3]=1.C(N(CC)CC)C.O(S(C)(=O)=O)S(C)(=O)=O.C(O)(=O)C(O)=O.[NH2:52][C:53]1[CH:54]=[CH:55][C:56](=[O:60])[N:57]([CH3:59])[CH:58]=1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:52][C:53]2[CH:54]=[CH:55][C:56](=[O:60])[N:57]([CH3:59])[CH:58]=2)[C:9]2[C:10]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[N:11][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:13]=2[CH3:14])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 81560Methanesulfonic anhydrideHCID 102200045-Amino-1-methylpyridin-2(1H)-one oxalateHCID 117702762ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(4-methoxybenzyl)-5-methyl-1H-pyrazole-3-carboxylate

Product 1

HCID 117703005ethyl 4-((4-chlorophenyl)(1-methyl-6-oxo-1,6-dihydropyridin-3-ylamino)methyl)-1-(4-methoxybenzyl)-5-methyl-1H-pyrazole-3-carboxylateYield 28%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of Ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(4-methoxybenzyl)-5-methyl-1H-pyrazole-3-carboxylate (Step 1.3) (423 mg, 1.020 mmol) and triethylamine (1.42 mL, 10.20 mmol) in CH2Cl2 under Ar was added Ms2O (355 mg, 2.039 mmol) at −10° C. The reaction mixture was stirred for 30 min at this temperature. 5-Amino-1-methyl-2(1H)-pyridinone oxalate salt (218 mg, 1.020 mmol) was added at 30° C. After 1 hr, the reaction mixture was quenched with a saturated aq. NaHCO solution, and extracted with CH2Cl2. The combined organic layers were washed a saturated aqueous solution of NaHCO3, dried over Na2SO4 and evaporated. The crude material was purified by silica gel column chromatography (CH2Cl2/MeOH 1-2%) to afford the title product (147 mg, 0.282 mmol, 28% yield) as a greenish solid. tR: 4.68 min (HPLC 1); tR: 1.06 min (LC-MS 2); ESI-MS: 521 [M+H]+ (LC-MS 2); Rf=0.56 (CH2Cl2/MeOH 9:1).

Workup

  1. waitAfter 1 hr
  2. customthe reaction mixture was quenched with a saturated aq. NaHCO solution
  3. extractionextracted with CH2Cl2
  4. washThe combined organic layers were washed a saturated aqueous solution of NaHCO3
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe crude material was purified by silica gel column chromatography (CH2Cl2/MeOH 1-2%)

Sources & evidence

ORD record
ord-9f4142d5a30b41eba76392e65c6caf0f
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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