N-methyl-2-pyrrolidone → HCID 51346966, compound

HRID 2088935Notes

Reaction equation

HRID 2088935 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.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[F:35][C:36]([F:58])([F:57])[CH2:37][CH2:38][C:39]1[N:40]=[C:41]([CH:51]2[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]2)[N:42]([CH2:44][CH2:45][N:46]2[CH2:50][CH2:49][CH2:48][CH2:47]2)[CH:43]=1.CN1CCCC1=O.C(N(C(C)C)CC)(C)C>O>[CH3:12][C@H:11]1[C:3]2[C:2]([N:54]3[CH2:55][CH2:56][CH:51]([C:41]4[N:42]([CH2:44][CH2:45][N:46]5[CH2:47][CH2:48][CH2:49][CH2:50]5)[CH:43]=[C:39]([CH2:38][CH2:37][C:36]([F:57])([F:35])[F:58])[N:40]=4)[CH2:52][CH2:53]3)=[N:7][CH:6]=[N:5][C:4]=2[NH:8][C:9](=[O:13])[CH2:10]1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 86666575(R)-4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-oneHCID 86666583HCID 86666583, compound

Product 1

HCID 51346966HCID 51346966, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
200 °C

Procedure

Add (R)-4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (0.33 g, 1.66 mmol), 4-(4-(3,3,3-trifluoropropyl)-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine tris(2,2,2-trifluoroacetate) (1.12 g, 1.0 eq), N-methylpyrrolidinone (10 mL) and diisopropylethylamine (2.30 mL, 8.0 eq) in a microwave tube. Seal with crimp cap. Heat in a microwave reactor at 200° C. for 10 minutes. Dilute the reaction mixture with water and extract with ethyl acetate. Wash with saturated aqueous sodium chloride. Dry the organics over anhydrous sodium sulfate, filter, and concentrate in vacuo. Purify by normal phase chromatography, eluting with hexanes to 10% methanol/dichloromethane, to give the title compound, (R)-5-methyl-4-(4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(3,3,3-trifluoropropyl)-1H-imidazol-2-yl)piperidin-1-yl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one, as an amber solid (0.23 g, 27%). MS (ES) m/z=506 [M]+.

Workup

  1. customSeal with crimp cap
  2. extractionextract with ethyl acetate
  3. washWash with saturated aqueous sodium chloride
  4. dry with materialDry the organics over anhydrous sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by normal phase chromatography
  8. washeluting with hexanes to 10% methanol/dichloromethane

Sources & evidence

ORD record
ord-e342e3dc4de1447db0c0b5d74f2d8521
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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