Pyridine → HCID 59239574, compound

HRID 1697947Notes

Reaction equation

HRID 1697947 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[N:7]1[CH2:16][CH2:15][C:14]2[C:13]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[N:12][C:11]([C:23]3[CH:28]=[CH:27][C:26]([N+:29]([O-])=O)=[CH:25][CH:24]=3)=[N:10][C:9]=2[CH2:8]1.C([O:34]C(OCC)CN)C.[N:41]1[CH:46]=CC=[CH:43][CH:42]=1>>[CH2:42]([NH:41][C:46]([NH:29][C:26]1[CH:27]=[CH:28][C:23]([C:11]2[N:12]=[C:13]([N:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)[C:14]3[CH2:15][CH2:16][N:7]([C:3]4[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=4)[CH2:8][C:9]=3[N:10]=2)=[CH:24][CH:25]=1)=[O:34])[CH3:43]

Participants

4

Reactant 3

HCID 1049PyridineHCID 695242,2-DiethoxyethylamineHCID 59239245HCID 59239245, compound

Product 1

HCID 59239574HCID 59239574, compoundYield 57%

Conditions

Temperature
115 °C

Procedure

Step 3—Synthesis of 4-(7-(1-methyl-1H-imidazol-2-yl)-2-(4-nitrophenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)morpholine (mp): To a solution of product mo from step 2 (260 mg, 0.5 mmol) in pyridine (3 mL) was added dropwise 2,2-diethoxyethanamine (82 μL, 0.6 mmol) at rt. The resulting solution was heated at 115° C. for 3.5 hrs. After the reaction mixture cooled, it was concentrated in vacuo. The residue was treated with 2 N aqueous HCl (2.5 mL), and heated to reflux for 1 hr. The reaction solution was then cooled, and diluted with H2O, made basic with sat. aq. NaHCO3, extracted with EtOAc (3×10 mL). The combined organics were dried over Magnesium sulfate, filtered, concentrated onto Celite, and chromatographed (ISCO, 12 g column, 0-5% MeOH/EtOAc) to afford 113 mg (57%) of desired compound mp as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.59-8.53 (m, 2H), 8.32-8.26 (m, 2H), 6.83 (d, J=1.4, 1H), 6.74 (d, J=1.4, 1H), 4.38 (s, 2H), 3.91-3.85 (m, 4H), 3.62-3.56 (m, 7H), 3.38 (t, J=5.4, 2H), 2.90-2.84 (m, 2H). LC-MS: m/z=+422 (M+H)+.

Workup

  1. temperatureAfter the reaction mixture cooled
  2. concentrationit was concentrated in vacuo
  3. additionThe residue was treated with 2 N aqueous HCl (2.5 mL)
  4. temperatureheated
  5. temperatureto reflux for 1 hr
  6. temperatureThe reaction solution was then cooled
  7. additiondiluted with H2O
  8. extractionextracted with EtOAc (3×10 mL)
  9. dry with materialThe combined organics were dried over Magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated onto Celite
  12. customchromatographed (ISCO, 12 g column, 0-5% MeOH/EtOAc)

Sources & evidence

ORD record
ord-b9be9077e0e34b9f80291974c369911a
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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