4-Methylmorpholine → HCID 178501311, compound

HRID 1957568Notes

Reaction equation

HRID 1957568 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.[NH:41]1[CH2:45][C@@H:44]([C:46]([O:48][CH3:49])=[O:47])[CH2:43][C@@H:42]1[C:50]([O:52][CH3:53])=[O:51]>CN(C)C=O>[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]([N:41]4[CH2:45][C@@H:44]([C:46]([O:48][CH3:49])=[O:47])[CH2:43][C@@H:42]4[C:50]([O:52][CH3:53])=[O:51])=[O:21])=[CH:16][CH:15]=3)[CH2:9][NH:8][C:6]=2[N:7]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 53712375HCID 53712375, compoundHCID 178508889HCID 178508889, compound

Product 1

HCID 178501311HCID 178501311, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a sample of 225 mg (0.70 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 3.5 mL anhydrous dimethylformamide and 0.08 mL (0.72 mmol) of N-methylmorpholine. The reaction mixture was stirred at room temperature and 135 mg (0.77 mmol) 2-chloro-4,6-dimethoxy-1,3,5-triazine were added at once. The reaction was stirred for 0.5 hours at room temperature, and 213 mg (1.14 mmol) of trans-dimethyl pyrrolidine-2,4-dicarboxylate were added in 1.0 mL of dimethylformamide. After stirring at room temperature for another 3.5 hours, the reaction was concentrated in vacuo and chromatographed on silica gel with 2-8% CH3OH/CHCl3 to give 185 mg (54%) of trans-dimethyl 1-{5-[2-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)-ethyl]thien-2-ylcarbonyl}pyrrolidine-2,4-dicarboxylate as a tan solid. Mass Spectrum (FAB+): M+1=490; 1H NMR (300 MHz, DMSO) δ: 1.54-1.64 (m, 3H); 1.76-1.84 (m, 1H); 2.11-2.29 (m, 3H); 2.36-2.43 (m,--1H); 2.72-2.79 (m, 1H); 2.86-2.88 (m, 2H); 3.07-3.23 (m, 2H); 3.61 (s, 6H); 3.95-4.08 (m, 2H); 4.49-4.54 (M, 1H); 5.92 (s, 2H); 6.24 (d, J=1.6 Hz, 1H); 6.91-6.92 (m, 1H); 7.48 (d, J=2.4 Hz, 1H).

Workup

  1. stirringThe reaction was stirred for 0.5 hours at room temperature
  2. stirringAfter stirring at room temperature for another 3.5 hours
  3. concentrationthe reaction was concentrated in vacuo
  4. customchromatographed on silica gel with 2-8% CH3OH/CHCl3

Sources & evidence

ORD record
ord-e5ea0a8d8e654a9db751e9856441a228
Source dataset
uspto-grants-1998_07
Patent number
US05786358

Reaction notes

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