4-Methylmorpholine → HCID 178442253, compound

HRID 2050536Notes

Reaction equation

HRID 2050536 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([OH:8])[C:5]([CH2:9][CH2:10][CH2:11][C:12]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=2)=[CH2:13])=[C:4]([NH2:23])[N:3]=1.CN1CCOCC1.COC1N=C(OC)N=C(Cl)N=1.Cl.[CH3:43][O:44][C:45](=[O:54])[C@H:46]([CH2:48][CH2:49][C:50]([O:52][CH3:53])=[O:51])[NH2:47]>O1CCCC1>[NH2:1][C:2]1[N:7]=[C:6]([OH:8])[C:5]([CH2:9][CH2:10][CH2:11][C:12]([C:14]2[CH:15]=[CH:16][C:17]([C:18]([NH:47][C@H:46]([C:45]([O:44][CH3:43])=[O:54])[CH2:48][CH2:49][C:50]([O:52][CH3:53])=[O:51])=[O:20])=[CH:21][CH:22]=2)=[CH2:13])=[C:4]([NH2:23])[N:3]=1

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 12917568Dimethyl L-glutamate hydrochlorideHCID 178442254HCID 178442254, compound

Product 1

HCID 178442253HCID 178442253, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 270 mg (1 eq) of 4-[5-(2,6-diamino-4-hydroxypyrimidin-5-yl)-pent-1-en-2-yl]benzoic acid and 104 mg (1.2 eq) of N-methylmorpholine in 4.0 ml of anhydrous tetrahydrofuran, was vigorously stirred for 5 minutes at room temperature. To this mixture, 165 mg (1.1 eq) of 2,4-dimethoxy-6-chloro-1,3,5-triazine were added and the sol was stirred for 40 minutes at room temperature. An additional 104 mg (1.2 eq) of N-methylmorpholine were introduced followed by 236 mg (1.3 eq) of dry dimethyl-L-glutamate hydrochloride. The solution then was continuously stirred for 4 hours at room temperature. The solvent was removed under reduced pressure and the residue dissolved in chloroform. Extraction with saturated aqueous sodium bicarbonate removed unreacted acid, triazine and triazinone. The organic layer was dried over magnesium sulfate, filtered and evaporated to dryness to yield the product which was further purified by flash chromatography eluting with 1:10 methanol:chloroform. M.S.:m/z=471.2081 (M+, calc. for C23H29N5O6 : 471.2118). 1H-N.M.R. (CDCl3, 300 MHz): 1.41(quin, 2H, CH2 --CH2 --CH2, J=7.5 Hz); 2.00-2.55(m, 8H, 4×--CH2 --); 3.56(s, 3H, CH3O); 3.68(s, 3H, CH3O); 4.68 (dt, 1H, CH, J=6, 7.5 Hz); 4.84 (s (broad), 2H, NH2); 4.97 (s, 1Holef.); 5.18 (s, 1Holef.); 5.86 (s (broad), 2H, NH2); 7.29 (d, 2Harom., J=9 Hz); 7.62 (m, (broad), 1H, NHglu); 7.64 (d, 2Harom., J=9 Hz); 11.20 (s (broad), 1H, NHpyr).

Workup

  1. stirringthe sol was stirred for 40 minutes at room temperature
  2. stirringThe solution then was continuously stirred for 4 hours at room temperature
  3. customThe solvent was removed under reduced pressure
  4. dissolutionthe residue dissolved in chloroform
  5. extractionExtraction with saturated aqueous sodium bicarbonate removed unreacted acid, triazine and triazinone
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customto yield the product which
  10. customwas further purified by flash chromatography
  11. washeluting with 1:10 methanol

Sources & evidence

ORD record
ord-dfc27362bf28429585444ba5ff861d19
Source dataset
uspto-grants-1991_05
Patent number
US05013738

Reaction notes

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