Hydrochloric Acid → isopropyl 1-methyl-5-(2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1H-pyrazole-4-carboxylate

HRID 1802176Notes

Reaction equation

HRID 1802176 reaction equation
[CH3:1][N:2]1[C:6]([C:7](=[O:24])[NH:8][C:9]2[CH:14]=[CH:13][N:12]3[N:15]=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:17]=[C:11]3[CH:10]=2)=[C:5]([C:25]([OH:27])=[O:26])[CH:4]=[N:3]1.[CH3:28][CH:29](O)[CH3:30].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.Cl>CN(C)C=O.CN(C)C1C=CN=CC=1>[CH3:1][N:2]1[C:6]([C:7](=[O:24])[NH:8][C:9]2[CH:14]=[CH:13][N:12]3[N:15]=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:17]=[C:11]3[CH:10]=2)=[C:5]([C:25]([O:27][CH:29]([CH3:30])[CH3:28])=[O:26])[CH:4]=[N:3]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 8471TriethylamineHCID 2733179PyBroPHCID 573789541-methyl-5-(2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 57377632isopropyl 1-methyl-5-(2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1H-pyrazole-4-carboxylateYield 9.96%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A white suspension of 1-methyl-5-(2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1H-pyrazole-4-carboxylic acid (90 mg, 248 mol.) and 2-propanol (23 l, 298 mol) in N,N-dimethylformamide (2 ml) is cooled to 0° C. A solution of 4-dimethylaminopyridine (15.2 mg, 124 mol, 0.5 eq.) and PYBROP (127 mg, 273 mol, 1.1 eq.) in N,N-dimethylformamide (2 ml) is dropwise added at 0° C. followed after 5 min by triethylamine (105 l, 745 mol). The white suspension is allowed to warm to room temperature giving a colorless clear solution and stirred for 4.5 days. The colorless solution is poured on water, neutralized to pH 7-8 with aqueous 1N hydrochloric acid and extracted with dichloromethane (3×70 ml). The combined aqueous layer is washed with water (3×50 ml), dried with magnesium sulfate and the solvent is removed in vacuo. Purification of the residue (77 mg) by chromatography on a 10 g silica cartridge (eluent heptane/ethyl acetate 30-60% 25′) affords isopropyl 1-methyl-5-(2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1H-pyrazole-4-carboxylate (10 mg, 9.96%) as a white solid. MS: m/z=405.3 (M+H+).

Workup

  1. temperatureto warm to room temperature
  2. customgiving a colorless clear solution
  3. additionThe colorless solution is poured on water
  4. extractionextracted with dichloromethane (3×70 ml)
  5. washThe combined aqueous layer is washed with water (3×50 ml)
  6. dry with materialdried with magnesium sulfate
  7. customthe solvent is removed in vacuo
  8. customPurification of the residue (77 mg) by chromatography on a 10 g silica cartridge (eluent heptane/ethyl acetate 30-60% 25′)

Sources & evidence

ORD record
ord-8fda0dc013e84cda8ed88ca433047f62
Source dataset
uspto-grants-2013_01
Patent number
US08349824B2

Reaction notes

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