Diisopropylethylamine → HCID 86651587, compound

HRID 2386263Notes

Reaction equation

HRID 2386263 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([NH:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][N:3]=1.Cl.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH:18]1[C:23](O)=[O:24].CCN(C(C)C)C(C)C>CS(C)=O.O.CCOCC.CCO>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:9]([CH:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[C:23](=[O:24])[CH:18]3[CH2:19][O:20][CH2:21][CH2:22][N:17]3[C:6]=2[N:7]=1

Participants

8

Reactant 3

HCID 81531DiisopropylethylamineHCID 45790954Morpholine-3-carboxylic acid hydrochlorideHCID 86651586HCID 86651586, compound

Product 1

HCID 86651587HCID 86651587, compoundYield 20.4%

Reagents, catalysts & solvents 4

HCID 702EthanolCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

In a 100 mL round bottomed flask containing 2,4-dichloro-N-(tetrahydro-2H-pyran-4-yl)pyrimidin-5-amine (0.336 g, 1.354 mmol) in 2.0 mL of DMSO was added morpholine-3-carboxylic acid hydrochloride (0.295 g, 1.761 mmol) and DIPEA (1.183 ml, 6.77 mmol). The reaction mixture was stirred at 100° C. for 16 h. The reaction was cooled to room temperature, diluted with 30 mL of water, transferred to an appropriate separatory funnel and extracted with EtOAc (3×25 mL). The organic layers were combined, washed with sat. NaCl, dried over Na2SO4, filtered and concentrated in vacuo affording an oil. The oil was suspended in 10 mL of Et2O, added 2 drops of EtOH and sonicated until a yellow precipitate appeared. Let mixture sit at room temperature for 1 h, collected solids by vacuum filtration, washed with additional Et2O, hexanes and dried under high vacuum affording 2-chloro-5-(tetrahydro-2H-pyran-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one. (90 mg, 20.4% yield) as a light yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.54-1.65 (m, 1H) 1.70 (dd, J=12.88, 2.02 Hz, 1H) 2.51-2.70 (m, 2H) 3.03 (ddd, J=13.58, 12.32, 3.92 Hz, 1H) 3.41-3.66 (m, 4H) 4.03 (dd, J=11.87, 3.79 Hz, 4H) 4.32-4.47 (m, 2H) 4.59 (tt, J=12.47, 4.07 Hz, 1H) 8.05 (s, 1H). MS [M+H] found 325.2.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customtransferred to an appropriate separatory funnel
  3. extractionextracted with EtOAc (3×25 mL)
  4. washwashed with sat. NaCl
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customaffording an oil
  9. customsonicated until a yellow precipitate
  10. waitsit at room temperature for 1 h
  11. customcollected solids
  12. filtrationby vacuum filtration
  13. washwashed with additional Et2O, hexanes
  14. customdried under high vacuum

Sources & evidence

ORD record
ord-3cd38c38bd11458999a97dcae4dcc587
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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