Triethylamine → HCID 52913954, compound

HRID 2088940Notes

Reaction equation

HRID 2088940 reaction equation
[CH2:1]([C:3]1[N:4]=[C:5]([CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[N:6]([CH2:8][CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:7]=1)[CH3:2].Cl[C:22]1[C:23]2[C@H:31]([CH3:32])[CH2:30][C:29](=[O:33])[NH:28][C:24]=2[N:25]=[CH:26][N:27]=1.C(N(CC)CC)C.[OH-].[Na+]>C(OCC)(=O)C.O.CN1CCCC1=O>[CH2:1]([C:3]1[N:4]=[C:5]([CH:15]2[CH2:16][CH2:17][N:18]([C:22]3[C:23]4[C@H:31]([CH3:32])[CH2:30][C:29](=[O:33])[NH:28][C:24]=4[N:25]=[CH:26][N:27]=3)[CH2:19][CH2:20]2)[N:6]([CH2:8][CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:7]=1)[CH3:2]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 671120884-(4-ethyl-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidineHCID 86666575(R)-4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 52913954HCID 52913954, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
110 °C

Procedure

Combine 4-(4-ethyl-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine (7.70 g, 27.86 mmol), (R)-4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (6.06 g, 1.1 eq), N-methylpyrrolidinone (25.4 mL) and triethylamine (4.27 mL, 1.1 eq). Stir overnight at 110° C. under nitrogen, then let cool to room temperature. Dilute with ethyl acetate and water. Adjust the pH with 2 M aqueous sodium hydroxide to 10. Separate the layers. Wash the aqueous phase with ethyl acetate. Wash the organics with aqueous saturated sodium chloride. Concentrate the organics in vacuo. Dilute with ethyl acetate and water. Adjust the pH to 5. Separate the layers; discard the organic layer. Adjust the pH of the aqueous phase with 2 M aqueous sodium hydroxide to 11. Wash the aqueous phase with ethyl acetate. Wash the organics with water and aqueous saturated sodium chloride. Concentrate the organics in vacuo. Dilute with 2-methyltetrahydrofuran:hexanes (15:85, 77 mL). Stir overnight at room temperature. Filter and dry the resulting white solid under vacuum to give the title compound, (R)-4-(4-(4-ethyl-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidin-1-yl)-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (7.90 g, 65%). MS (ES) m/z=438 [M]+.

Workup

  1. temperaturelet cool to room temperature
  2. customSeparate the layers
  3. washWash the aqueous phase with ethyl acetate
  4. washWash the organics with aqueous saturated sodium chloride
  5. concentrationConcentrate the organics in vacuo
  6. additionDilute with ethyl acetate and water
  7. customSeparate the layers
  8. washWash the aqueous phase with ethyl acetate
  9. washWash the organics with water and aqueous saturated sodium chloride
  10. concentrationConcentrate the organics in vacuo
  11. additionDilute with 2-methyltetrahydrofuran:hexanes (15:85, 77 mL)
  12. stirringStir overnight at room temperature
  13. filtrationFilter
  14. customdry the resulting white solid under vacuum

Sources & evidence

ORD record
ord-d22ec4e807d34e12be463a655bb53f76
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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