Triethylamine → HCID 13478346, compound

HRID 371460Notes

Reaction equation

HRID 371460 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[C:4]([CH3:24])[N:3]=1.P(C#N)(=O)(OCC)OCC.C(N(CC)CC)C.Cl.[CH3:43][O:44][C:45](=[O:48])[CH2:46][NH2:47]>CN(C)C=O>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N:9]2[CH2:10][CH2:11][N:12]([C:15]3[CH:16]=[CH:17][C:18]([C:19]([NH:47][CH2:46][C:45]([O:44][CH3:43])=[O:48])=[O:21])=[CH:22][CH:23]=3)[CH2:13][CH2:14]2)=[C:4]([CH3:24])[N:3]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 76257Diethyl cyanophosphonateHCID 122755Glycine methyl ester hydrochlorideHCID 9840389HCID 9840389, compound

Product 1

HCID 13478346HCID 13478346, compoundYield 54.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 3.9 g (0.012 mole) of 4-[4-(2,4-diamino-6-methyl-5-pyrimidinyl)-1-piperazinyl]benzoic acid, 6.5 g (0.039 mole) of diethyl phosphorocyanidate and 6.6 ml (0.047 mole) of triethyl amine in 500 ml of N,N-dimethylformamide (dried over 4H molecular sieves overnight) was stirred at room temperature for five hours. A mixture of 1.8 g (0.014 mole) of glycine methyl ester, hydrochloride, 2 ml (0.014 mole) of triethylamine and 10 ml of N,N-dimethylformamide was added to the suspension and the mixture was stirred at room temperature for another two hours. The solvent was removed under high vacuum (0.1 mm, dry ice-2-propanol trap) at 48° C. The solid residue was dissolved in 200 ml of ice water and neutralized with saturated sodium carbonate solution to pH 8. The solid was collected and washed with 100 ml of water. Recrystallization from acetonitrile gave 2.6 g of the product as a pale yellow solid, mp 255° C. (with decomposition).

Workup

  1. additionwas added to the suspension
  2. stirringthe mixture was stirred at room temperature for another two hours
  3. customThe solvent was removed under high vacuum (0.1 mm, dry ice-2-propanol trap) at 48° C
  4. dissolutionThe solid residue was dissolved in 200 ml of ice water and neutralized with saturated sodium carbonate solution to pH 8
  5. customThe solid was collected
  6. washwashed with 100 ml of water
  7. customRecrystallization from acetonitrile

Sources & evidence

ORD record
ord-e4b140134b0c496297abfabb25123591
Source dataset
uspto-grants-1985_07
Patent number
US04532240

Reaction notes

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