Ethyl 4-chloro-2-methylpyrimidine-5-carboxylate → Ethyl 2-methyl-4-{N-butyl-N-[{2'-(N-triphenylmethyltetrazol-5-yl)biphenyl-4-yl}methyl]amino}pyrimidine-5-carboxylate

HRID 1030061Notes

Reaction equation

HRID 1030061 reaction equation
[C:1]1([C:7]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]3[CH:24]=[CH:23][C:22]([CH2:25][NH:26][CH2:27][CH2:28][CH2:29][CH3:30])=[CH:21][CH:20]=3)=[N:11][N:10]=[N:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:43]([O:45][C:46]([C:48]1[C:49](Cl)=[N:50][C:51]([CH3:54])=[N:52][CH:53]=1)=[O:47])[CH3:44]>C1COCC1.C(N(CC)CC)C>[CH3:54][C:51]1[N:50]=[C:49]([N:26]([CH2:27][CH2:28][CH2:29][CH3:30])[CH2:25][C:22]2[CH:23]=[CH:24][C:19]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]3[N:8]([C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)[C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:9]=[N:10][N:11]=3)=[CH:20][CH:21]=2)[C:48]([C:46]([O:45][CH2:43][CH3:44])=[O:47])=[CH:53][N:52]=1

Participants

5

Reactant 2

HCID 12677176Ethyl 4-chloro-2-methylpyrimidine-5-carboxylateHCID 19821739N-Triphenylmethyl-5-(4'-butylaminomethylbiphenyl-2-yl)tetrazole

Product 1

HCID 19791910Ethyl 2-methyl-4-{N-butyl-N-[{2'-(N-triphenylmethyltetrazol-5-yl)biphenyl-4-yl}methyl]amino}pyrimidine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

The product of Example 1A was dissolved in 15 ml of THF containing 4.6 ml of triethylamine. A solution of 1.94 g (9.7 mmoles) of ethyl-2-methyl-4-chloropyrimidine-5-carboxylate (E. Peters, et al., J. Org. Chem. 25 2137 (1960)) in 2 ml of THF was added and the resulting solution was stirred at room temperature for 2 hours. The solution was then concentrated and the resulting residue was dissolved in toluene. The toluene solution was extracted with potassium bicarbonate, dried over sodium sulfate and concentrated. The crude product was chromatographed on silica gel eluting with 12% ethyl acetate/88%toluene to provide 4.97 g of the desired product, which was crystallized from ether/hexane (1:1). M.p. 130°-132° C.

Workup

  1. concentrationThe solution was then concentrated
  2. dissolutionthe resulting residue was dissolved in toluene
  3. extractionThe toluene solution was extracted with potassium bicarbonate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was chromatographed on silica gel eluting with 12% ethyl acetate/88%toluene

Sources & evidence

ORD record
ord-5498374cdf08456bb3e5493066efbb95
Source dataset
uspto-grants-1992_04
Patent number
US05104877

Reaction notes

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