4-Methylmorpholine → HCID 178471584, compound

HRID 2074035Notes

Reaction equation

HRID 2074035 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([OH:8])[C:5]([CH2:9][CH2:10][CH2:11][CH2:12][C:13]2[CH:14]=[C:15](C(O)=O)[S:16][CH:17]=2)=[C:4]([NH2:21])[N:3]=1.C1(NP(Cl)[O:30][C:31]2C=CC=CC=2)C=CC=CC=1.CN1CC[O:42]CC1.Cl.[NH2:46][C@H:47]([C:55]([O:57][CH2:58][CH3:59])=[O:56])[CH2:48][CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51]>CN1CCCC1=O>[NH2:1][C:2]1[N:7]=[C:6]([OH:8])[C:5]([CH2:9][CH2:10][CH2:11][CH2:12][C:13]2[CH:14]=[C:15]([O:42][C:31]([NH:46][C@H:47]([C:55]([O:57][CH2:58][CH3:59])=[O:56])[CH2:48][CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51])=[O:30])[S:16][CH:17]=2)=[C:4]([NH2:21])[N:3]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 73960Glutamic acid diethyl ester hydrochlorideHCID 19856113HCID 19856113, compoundHCID 178508749HCID 178508749, compound

Product 1

HCID 178471584HCID 178471584, compoundYield 54.2%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A 25 mL round bottomed flask, equipped with a magnetic stirrer and gas inlet, was charged with 0.15 g (1.0 eq) of 4-[4-(2,6-diamino-4-hydroxypyrimidin-5-yl)butyl]thien-2-ylcarboxylic acid, 0.20 g (1.5 eq) of phenyl N-phenylphosphoramidochloridite, 0.25 g (5.0 eq) of N-methylmorpholine, and 15 mL of anhydrous N-methylpyrrolidone. The mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. To the resulting homogeneous solution was added 0.23 g (2.0 eq) of diethyl L-glutamate hydrochloride and stirring under nitrogen was continued for 24 hours. The solvent was removed by vacuum distillation and chloroform was added to the residue. The chloroform solution was washed with water. The organic extracts were combined, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification was carried out by flash chromatography eluting with 10% methanol/chloroform. Fractions homogeneous by TLC for the major component were combined and concentrated under reduced pressure to give 0.13 g (54.2%) of diethyl N-(4-[4-(2,6-diamino-4-hydroxypyrimidin-5-yl)butyl]thien-2-ylcarboxy)-L-glutamate as a pale yellow powder, m,p,: 94°-96° C.; IR (KBr, cm-1): 3368, 3363, 3361, 3358, 3352, 3349, 3346, 3343, 1735, 1560, 1552, 1525, 1499, 1447, 1428, 1371, 1206, 1180; UV (Ethanol): λmax =278 nm (epsilon=19,700), 248 nm (epsilon=13,300), 211 nm (epsilon=23,900), 1H NMR (CDCl3, 300 MHz) delta 7.94 (s, 1H), 7.85 (d,J=7.8 Hz, 1H), 7.08 (s, 1H), 5.11 (bs, 2H), 4.67-4.73 (m, 1H) 4.55 (bs, 2H), 4.23 (q, J=7.2 Hz, 2H), 4.15 (q, J=7.2 Hz, 2H), 2.66-2.71 (m, 2H), 2.56-2.61 (m, 2H), 2.23-2.44 (m, 4H), 1.59-1.70 (m, 2H), 1.44-1.51 (m, 2H), 1.25-1.32 (m, 6H); MASS: M+ =494 (FD).

Workup

  1. customA 25 mL round bottomed flask, equipped with a magnetic stirrer and gas inlet
  2. stirringstirring under nitrogen
  3. waitwas continued for 24 hours
  4. customThe solvent was removed by vacuum distillation and chloroform
  5. additionwas added to the residue
  6. washThe chloroform solution was washed with water
  7. dry with materialdried (magnesium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification
  11. washeluting with 10% methanol/chloroform
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-473a55d98e684fdfa6e657d007783629
Source dataset
uspto-grants-1990_04
Patent number
US04920125

Reaction notes

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