Triethylamine → 4-(benzyloxy)-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxylic acid

HRID 1470311Notes

Reaction equation

HRID 1470311 reaction equation
NC1C(O)=NC(N2C=CC=N2)=NC=1.[CH2:14]([O:21][C:22]1[C:27]([C:28]([OH:30])=[O:29])=[CH:26][N:25]=[C:24]([N:31]2[CH:35]=[CH:34][CH:33]=[N:32]2)[N:23]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(Cl)(=O)C(Cl)=O.CCN(CC)CC.[N-:49]=[N+:50]=[N-:51].[Na+]>ClCCl.CN(C=O)C.O>[CH2:14]([O:21][C:22]1[C:27]([C:28]([OH:30])=[O:29])=[CH:26][N:25]=[C:24]([N:31]2[CH:35]=[CH:34][CH:33]=[N:32]2)[N:23]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1.[N:49]([C:28]([C:27]1[C:22]([O:21][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:23][C:24]([N:31]2[CH:35]=[CH:34][CH:33]=[N:32]2)=[N:25][CH:26]=1)=[O:29])=[N+:50]=[N-:51]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 33557Sodium AzideHCID 65578Oxalyl chlorideHCID 674594834-(benzyloxy)-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxylic acid2×HCID 178508031HCID 178508031, compound

Product 2

HCID 674594834-(benzyloxy)-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxylic acidHCID 89372972Azido(4-(benzyloxy)-2-(1H-pyrazol-1-yl)pyrimidin-5-yl)methanone

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

4-(benzyloxy)-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxylic acid (3-c) was synthesized in a manner outlined in Steps A through Step C of the synthesis of Intermediate 3-e. To a solution of 4-(benzyloxy)-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxylic acid, 3-c, (500 mg, 1.69 mmol) in dry dichloromethane (10 ml) was added dropwise oxalyl chloride (0.29 ml, 3.38 mmol) at 0° C. and a catalytic amount of DMF (3-5 drops). The mixture was stirred at room temperature for 3 hours. Then the mixture was concentrated under vacuum and the residue was dissolved in acetone (10 ml). Et3N (205 mg, 2.03 mmol) was added at 0° C. and the mixture was stirred for 5 mins before sodium azide (988 mg, 15.2 mmol) in water (1 ml) was added. The resulting mixture was stirred at room temperature for 1 h. Subsequently, the mixture was diluted with water and filtered. The solid was washed with water (5-10 ml) and then taken into approximately 20-30 mL of dichloromethane. The organic layer was dried over sodium sulfate and concentrated under vacuum to provide compound 5-a as a solid (130 mg) which was used in Step B without any further purification. (M+H)+=322.

Workup

  1. concentrationThen the mixture was concentrated under vacuum
  2. dissolutionthe residue was dissolved in acetone (10 ml)
  3. additionwas added
  4. stirringThe resulting mixture was stirred at room temperature for 1 h
  5. filtrationfiltered
  6. washThe solid was washed with water (5-10 ml)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-84d984c822014756886b7e8c5f7aca90
Source dataset
uspto-grants-2015_04
Patent number
US09006433B2

Reaction notes

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