4-Methylmorpholine → HCID 178442472, compound

HRID 2050531Notes

Reaction equation

HRID 2050531 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([OH:8])[C:5]([CH2:9][CH2:10][CH2:11][CH:12]([C:15]2[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][CH:16]=2)[CH:13]=[CH2:14])=[C:4]([NH2:24])[N:3]=1.CN1CCOCC1.COC1N=C(OC)N=C(Cl)N=1.Cl.[CH3:44][O:45][C:46](=[O:55])[C@H:47]([CH2:49][CH2:50][C:51]([O:53][CH3:54])=[O:52])[NH2:48]>CN(C)C=O>[NH2:1][C:2]1[N:7]=[C:6]([OH:8])[C:5]([CH2:9][CH2:10][CH2:11][CH:12]([C:15]2[CH:16]=[CH:17][C:18]([C:19]([NH:48][C@H:47]([C:46]([O:45][CH3:44])=[O:55])[CH2:49][CH2:50][C:51]([O:53][CH3:54])=[O:52])=[O:20])=[CH:22][CH:23]=2)[CH:13]=[CH2:14])=[C:4]([NH2:24])[N:3]=1

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 12917568Dimethyl L-glutamate hydrochlorideHCID 178442473HCID 178442473, compound

Product 1

HCID 178442472HCID 178442472, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution containing 950 mg eq) of 4-[6-(2,6-diamino-4-hydroxypyrimidin-5-yl)hex-1-en-3-yl]benzoic acid as prepared in step F, 351 mg (1.2 eq) Of N-methylmorpholine, and 10.0 ml of anhydrous dimethylformamide, was vigorously stirred at ambient temperature for 5 minutes. To this solution was added 556 mg (1.1 eq) of 2,4-dimethoxy-6-chloro-1,3,5-triazine and this mixture was then stirred at room temperature for 40 minutes. Following additipn to the solution of 351 mg (1.3 eq) of N-methylmorpholine, and 795 mg (1.3 eq) of dry dimethyl-L-glutamate hydrochloride, the mixture was continuously stirred overnight at room temperature and the solvent then removed under reduced pressure. The product was dissolved in chloroform, and extracted with saturated aqueous sodium bicarbonate to remove unreacted acid, triazine and triazinone. The organic extract 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=485.2269 (M+, calc. for C24H31N5O6 : 485.2274). 1H-N.M.R. (CDCl3, 300 MHz): 1.03-1.35 (m, 2H, CH2 --CH2CH2); 1.62 (m, 2H, CH2 --CH--CH=); 2.15 (t, 2H, CH2 -pyr, J=7.5 Hz); 2.0-2.5 (m, 4H, 2×CH2(glu) ; 3.18 (m, 1H, CH--C=); 3.56 (s, 3H, CH3O); 3.66 (s, 3H, CH3O); 4.70 (m, 1H, CHglu); 4.8-5.0 (m, 2Holef.,); 4.89 (s (broad), 2H, NH2); 5.6-5.9 (m, 3H, NH2 +CH=CH2); 7.08 (d, 2Harom., J=8 Hz); 7.50 (m, 1H, NHglu); 7.63 (d, 2Harom., J=8 Hz); 11.25 (s (broad), 1H, NHpyr).

Workup

  1. stirringthis mixture was then stirred at room temperature for 40 minutes
  2. waitthe mixture was continuously stirred overnight at room temperature
  3. customthe solvent then removed under reduced pressure
  4. dissolutionThe product was dissolved in chloroform
  5. extractionextracted with saturated aqueous sodium bicarbonate
  6. customto remove unreacted acid, triazine and triazinone
  7. extractionThe organic extract
  8. dry with materialwas dried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated to dryness
  11. customto yield the product which
  12. customwas further purified by flash chromatography
  13. washeluting with 1:10 methanol

Sources & evidence

ORD record
ord-3fa2cc9807894058ac9d180688bc0f70
Source dataset
uspto-grants-1991_05
Patent number
US05013738

Reaction notes

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