4-Methylmorpholine → HCID 178472754, compound

HRID 1957560Notes

Reaction equation

HRID 1957560 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)=[CH:16][CH:15]=3)[CH2:9][NH:8][C:6]=2[N:7]=1.CN1CCOCC1.ClC1N=C(OC)N=C(OC)N=1.Cl.[CH2:42]([O:44][C:45](=[O:48])[CH2:46][NH2:47])[CH3:43]>CN(C)C=O>[CH2:42]([O:44][C:45](=[O:48])[CH2:46][NH:47][C:19]([C:17]1[S:18][C:14]([CH2:13][CH2:12][CH:10]2[CH2:9][NH:8][C:6]3[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([OH:22])[C:5]=3[CH2:11]2)=[CH:15][CH:16]=1)=[O:21])[CH3:43]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine3×HCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 2723640Glycine ethyl ester, hydrochloride2×HCID 178508889HCID 178508889, compound

Product 1

HCID 178472754HCID 178472754, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To 0.15 g (0.47 mmol) of 5-[2-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]-pyrimidin-6-yl)ethyl]thien-2-ylcarboxylic acid in a three-necked round bottomed flask under an atmosphere of nitrogen were added 3.0 mL of anhydrous dimethylformamide and 0.11 mL (0.99 mmol) of 4-methylmorpholine. To this was then added 0.84 g (0.48 mmol) of 2-chloro-4,6-dimethoxy-1,3,5-triazine. The reaction mixture was stirred at room temperature for 35 minutes and a solution of 0.072 g (0.51 mmol) of glycine ethyl ester hydrochloride in 1.0 mL of anhydrous dimethylformamide was added together with 0.65 mL (5.85 mmol) of 4-methylmorpholine. After 35 minutes, an additional 0.015 g (0.11 mmol) of glycine ethyl ester hydrochloride and 0.2 mL (1.80 mmol) of 4-methylmorpholine was added. The reaction was stirred for 3 hours and concentrated in vacua. The crude mixture then was chromatographed on silica gel eluting with a gradient of 2-12% CH3OH/CHCl3 to give 0.072 g (38%) of N-{5-[2-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)ethyl]thien-2-ylcarbonyl}glycine ethyl ester as a white solid. Rf=0.34 (20% CH3OH/CHCl3) m.p.=152°-160° C. (foam, dec.) Mass Spectrum (FD+): M+=405; IR (CHCl3, cm-1)=1046, 1196, 1304, 1464, 1602, 1745, 2363, 2977, 3025, 3619; UV (C2H5OH) λmax =222, 279 (ε=24333, 23816); 1H NMR (300 MHz, DMSOd6) δ1.17 (t, J=6.5 Hz, 3H), 1.52-1.60 (m, 3H), 1.77-1.84 (m, 1H), 2.40-2.44 (m, 1H), 2.72-2.8(m, 3H), 3.14-3-24 (m, 1H), 3.91 (d, J=4.7 Hz, 2H), 4.05-4.12 (m, 2H), 6.24 (s, 2H), 6.89 (s, 1H, 7.57 (s, 1H), 8.80 (s, 1H), 9.66 (s, 1H).

Workup

  1. waitAfter 35 minutes
  2. stirringThe reaction was stirred for 3 hours
  3. concentrationconcentrated in vacua
  4. customThe crude mixture then was chromatographed on silica gel eluting with a gradient of 2-12% CH3OH/CHCl3

Sources & evidence

ORD record
ord-86c12d8767ae439a8d0358c11cb3cfd7
Source dataset
uspto-grants-1998_07
Patent number
US05786358

Reaction notes

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