Triethylamine → (R)-5-Methyl-4-(4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

HRID 2088924Notes

Reaction equation

HRID 2088924 reaction equation
Cl[C:2]1[C:3]2[C@H:11]([CH3:12])[CH2:10][C:9](=[O:13])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C(N(CC)CC)C.[N:21]1([CH2:26][CH2:27][N:28]2[CH:32]=[C:31]([CH:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)[N:30]=[C:29]2[CH:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)[CH2:25][CH2:24][CH2:23][CH2:22]1.[OH-].[Na+]>C(OCC)(=O)C.O.CN1CCCC1=O>[CH3:12][C@H:11]1[C:3]2[C:2]([N:42]3[CH2:41][CH2:40][CH:39]([C:29]4[N:28]([CH2:27][CH2:26][N:21]5[CH2:22][CH2:23][CH2:24][CH2:25]5)[CH:32]=[C:31]([CH:33]5[CH2:34][CH2:35][O:36][CH2:37][CH2:38]5)[N:30]=4)[CH2:44][CH2:43]3)=[N:7][CH:6]=[N:5][C:4]=2[NH:8][C:9](=[O:13])[CH2:10]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 671119654-(1-(2-pyrrolidin-1-yl-ethyl)-4-(tetrahydro-pyran-4-yl)-1H-imidazol-2-yl)-piperidineHCID 86666575(R)-4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 67112053(R)-5-Methyl-4-(4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-2-yl)piperidin-1-yl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-oneYield 65.8%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

Combine (R)-4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (15.69 g, 1.2 eq), triethylamine (10.14 mL, 1.1 eq), 4-[1-(2-pyrrolidin-1-yl-ethyl)-4-(tetrahydro-pyran-4-yl)-1H-imidazol-2-yl]-piperidine (22 g, 66.17 mmol) and N-methylpyrrolidinone (66 mL). Stir at 110° C. for 16 hours, then allow to cool to room temperature. Dilute with ethyl acetate (110 mL) and water (220 mL). Add 5 M aqueous sodium hydroxide to adjust the pH to 12. Extract with ethyl acetate (2×200 mL). Wash the organics with saturated aqueous sodium chloride. Add water (220 mL) to the organics and aqueous 85% phosphoric acid to adjust the pH to 3. Wash the resulting acidic aqueous layer with ethyl acetate (2×100 mL). Add 5 M aqueous sodium hydroxide to adjust the pH to 12. Extract with ethyl acetate (3×70 mL). Wash the organics with saturated aqueous sodium chloride (50 mL). Dry the organics over anhydrous magnesium sulfate and concentrate in vacuo to give the final compound as a light brown solid (21.5 g, 64%). MS (ES) m/z=494 [M]+.

Workup

  1. temperatureto cool to room temperature
  2. extractionExtract with ethyl acetate (2×200 mL)
  3. washWash the organics with saturated aqueous sodium chloride
  4. washWash the resulting acidic aqueous layer with ethyl acetate (2×100 mL)
  5. additionAdd 5 M aqueous sodium hydroxide
  6. extractionExtract with ethyl acetate (3×70 mL)
  7. washWash the organics with saturated aqueous sodium chloride (50 mL)
  8. dry with materialDry the organics over anhydrous magnesium sulfate
  9. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-1957ae044428441f8bb83d02c8dfe44c
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

Loading…