4-Methylmorpholine → HCID 178508885, compound

HRID 1957562Notes

Reaction equation

HRID 1957562 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([OH:22])[C:5]2[CH2:11][CH:10]([CH2:12][CH2:13][C:14]3[S:18][C:17]([C:19]([OH:21])=[O:20])=[CH:16][CH:15]=3)[CH2:9][NH:8][C:6]=2[N:7]=1.C[N:24]1CCOCC1.[NH2:30][CH:31]([CH2:35][C:36]1[N:37]=[N:38][NH:39][N:40]=1)[C:32]([OH:34])=[O:33]>CN(C)C=O>[NH4+:1].[NH4+:24].[NH2:1][C:2]1[N:3]=[C:4]([OH:22])[C:5]2[CH2:11][CH:10]([CH2:12][CH2:13][C:14]3[S:18][C:17]([C:19]([NH:30][CH:31]([CH2:35][C:36]4[N:37]=[N:38][NH:39][N:40]=4)[C:32]([O-:34])=[O:33])=[O:21])=[CH:16][CH:15]=3)[CH2:9][NH:8][C:6]=2[N:7]=1.[NH2:1][C:2]1[N:3]=[C:4]([OH:22])[C:5]2[CH2:11][CH:10]([CH2:12][CH2:13][C:14]3[S:18][C:17]([C:19]([NH:30][CH:31]([CH2:35][C:36]4[N:37]=[N:38][NH:39][N:40]=4)[C:32]([O-:34])=[O:33])=[O:20])=[CH:16][CH:15]=3)[CH2:9][NH:8][C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 299876NSC173723HCID 178508889HCID 178508889, compound

Product 1

HCID 178508885HCID 178508885, compoundYield 27.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

After flame drying a 15 mL two-neck round bottom flask under argon, 0.18 g (0.57 mmol) of 5-[2-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)ethyl]-thien-2-ylcarboxylic acid was suspended in 2 mL of anhydrous N,N-dimethylformamide, followed by the addition of 0.19 mL (1.7 mmol) of 4-methylmorpholine. After allowing the reaction mixture to stir at room temperature for 15 minutes, 0.15 g (0.86 mmol) of 2-chloro-4,6-dimethoxyl,3,5-triazine was added. The reaction was stirred at room temperature for 30 minutes, 0.135 g (0.86 mmol) of amino-3-(2H-tetrazol-5-yl)propanoic acid was added, and the reaction mixture was stirred at room temperature for an additional 3 hours. The volatiles were removed in vacuo, and the residue was treated with 50 mL of water and the solid was filtered and dried in a vacuum oven at 60° C. The crude solid was purified using rotary chromatography on a 2 mm Chromatotron® silica gel plate, and eluted with a gradient of 20% CH3OH/CHCl3 to 60:30:10 CHCl3 /CH3OH/NH4OH. The correct fractions were combined and concentrated in vacuo to give 0.050 g (18%) of 2-{5-[2-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]-pyrimidin-6-yl)ethyl]thien-2-ylcarbonylamino}-3-(2H-tetrazol-5-yl)propanoic acid diammonium salt as a white solid. Rf 0.22 (5:3.5:1.5) (CHCl3 /CH3OH/NH4OH); m.p. 228° C. (foam); IR (KBr, cm-1)=553, 616, 746, 814, 1098, 1307, 1396, 1460, 1546, 1617, 3216; UV (0.1N NaOH) λmax =277, 217 (ε=19367, 19896); Exact Mass: Calcd=460.1515; Found=460.1508; 1H NM (300 MHz, DMSOd6) δ1.52-1.64 (m, 3H), 1.76-1.84 (m, 1H), 2.51-2.88 (m, 3H), 3.07-3.23 (m, 4H), 4.45-4.51 (m, 1H), 5.92 (s, 2H), 6.23 (s, 1H), 6.86 (d, J=3.1 Hz, 1H), 7.50 (d, J=3.4 Hz, 1H), 8.56 (d, J=7.3 Hz, 1H);

Workup

  1. temperatureAfter flame
  2. customdrying a 15 mL two-neck round bottom flask under argon
  3. stirringThe reaction was stirred at room temperature for 30 minutes
  4. stirringthe reaction mixture was stirred at room temperature for an additional 3 hours
  5. customThe volatiles were removed in vacuo
  6. additionthe residue was treated with 50 mL of water
  7. filtrationthe solid was filtered
  8. customdried in a vacuum oven at 60° C
  9. customThe crude solid was purified
  10. washeluted with a gradient of 20% CH3OH/CHCl3 to 60:30:10 CHCl3 /CH3OH/NH4OH
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-844128cddc914828a241aed10641ce4b
Source dataset
uspto-grants-1998_07
Patent number
US05786358

Reaction notes

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