4-Methylmorpholine → HCID 178508884, compound

HRID 1957563Notes

Reaction equation

HRID 1957563 reaction equation
Cl.[NH2:2][C:3]1[N:4]=[C:5]([OH:24])[C:6]2[CH2:12][CH:11]([CH2:13][CH2:14][C:15]3[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][CH:16]=3)[CH2:10][NH:9][C:7]=2[N:8]=1.CN1CCOCC1.ClC1N=C(OC)N=C(OC)N=1.[NH2:43][C:44]1([C:51]([OH:53])=[O:52])[CH2:49][CH:48]2[CH2:50][CH:45]1[CH2:46][CH2:47]2.[NH4+].CC(C([O-])=O)CCCCC.[K+].[Br-].[OH-].[Na+]>CN(C)C=O>[NH4+:2].[NH2:2][C:3]1[N:4]=[C:5]([OH:24])[C:6]2[CH2:12][CH:11]([CH2:13][CH2:14][C:15]3[CH:23]=[CH:22][C:18]([C:19]([NH:43][C:44]4([C:51]([O-:53])=[O:52])[CH2:49][CH:48]5[CH2:50][CH:45]4[CH2:46][CH2:47]5)=[O:20])=[CH:17][CH:16]=3)[CH2:10][NH:9][C:7]=2[N:8]=1

Participants

9

Reactant 7

HCID 79724-MethylmorpholineHCID 14798Sodium HydroxideHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 1152882-Aminonorbornane-2-carboxylic acidHCID 253877Potassium BromideHCID 131720774HCID 131720774, compoundHCID 178479160HCID 178479160, compound

Product 1

HCID 178508884HCID 178508884, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

After flame drying a 15-mL two-neck round bottom flask under argon, 0.20 g (0.57 mmol) of 4-[2-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)ethyl]-benzoic acid hydrochloride 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 stirring the reaction at room temperature for 15 minutes, 0.15 g (0.86 mmol) of 2-chloro-4,6-dimethoxy-1,3,5-triazine was added. The reaction was stirred at room temperature for 30 minutes and 0.134 g (0.86 mmol) of 2-aminonorbornane-2-carboxylic acid was added. The reaction mixture was stirred at room temperature for 3 hours. The volatiles were concentrated in vacuo, and the residue was treated with 50 mL of H20, and the white solid was filtered and dried in a vacuum oven at 60° C. The crude solid was purified using rotor chromatography on a 2 mm Chromatotron® silica gel plate, and eluted with a gradient of 20% CH3OH/CHCl3 to 75:25:1 CHCl3 /CH3OH/NH4OH. The correct fractions were combined and removed in vacuo to give 0.025 g (9%) of 2-{4-[2-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)ethyl]benzoylamino}bicyclo[2.2.]heptane-2-carboxylic acid ammonium salt as a white solid. Rf=0.30 (6/3.2/0.8) (CHCl3 /CH3OH/NH4OH); m.p. 241° C. (foam); IR (KBr, cm-1)=615, 647, 772, 1019, 1121, 1218, 1307, 1370, 1477, 1538, 1641, 2952, 3344; UV (0.1N NaOH) λmax =273, 241, 218 (ε=9839, 14408, 21458); Exact mass: Calcd=452.2298; Found=452.2338 5; 1H NMR (300 MHz, DMSOd6) δ1.26-1.37 (m, 2H), 1.48-1.81 (m, 7H), 1.84-1.88 (m, 4H), 2.63-2.83 (m, 4H), 3.19-3.27 (m, 2H), 5.97 (s, 2H), 6.27 (S, 1H), 7.31 (d, J=8.1 Hz, 2H), 7.78 (d, J=7.9 Hz, 2H), 8.53 (s, 1H).

Workup

  1. temperatureAfter flame
  2. customdrying a 15-mL two-neck round bottom flask under argon
  3. customthe reaction at room temperature for 15 minutes
  4. stirringThe reaction was stirred at room temperature for 30 minutes
  5. stirringThe reaction mixture was stirred at room temperature for 3 hours
  6. concentrationThe volatiles were concentrated in vacuo
  7. additionthe residue was treated with 50 mL of H20
  8. filtrationthe white solid was filtered
  9. customdried in a vacuum oven at 60° C
  10. customThe crude solid was purified
  11. washeluted with a gradient of 20% CH3OH/CHCl3 to 75:25:1 CHCl3 /CH3OH/NH4OH
  12. customremoved in vacuo
  13. customto give 0.025 g (9%) of 2-{4-[2-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)ethyl]benzoylamino}bicyclo[2.2

Sources & evidence

ORD record
ord-103999ad3d5640f8b357c7fbc71f427e
Source dataset
uspto-grants-1998_07
Patent number
US05786358

Reaction notes

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