N-methyl-2-pyrrolidone → HCID 86666580, compound

HRID 2088928Notes

Reaction equation

HRID 2088928 reaction equation
Cl[C:2]1[C:3]2[C@H:11]([C:12]([F:15])([F:14])[F:13])[CH2:10][C:9](=[O:16])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.Cl.Cl.[NH:19]1[CH2:24][CH2:23][CH:22]([C:25]2[N:26]([CH2:35][CH2:36][OH:37])[CH:27]=[C:28]([CH2:30][C:31]([F:34])([F:33])[F:32])[N:29]=2)[CH2:21][CH2:20]1.CN1CCCC1=O.C(N(C(C)C)CC)(C)C>C(=O)(O)[O-].[Na+]>[OH:37][CH2:36][CH2:35][N:26]1[CH:27]=[C:28]([CH2:30][C:31]([F:32])([F:34])[F:33])[N:29]=[C:25]1[CH:22]1[CH2:21][CH2:20][N:19]([C:2]2[C:3]3[C@H:11]([C:12]([F:15])([F:14])[F:13])[CH2:10][C:9](=[O:16])[NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 67112089HCID 67112089, compoundHCID 86666581HCID 86666581, compound

Product 1

HCID 86666580HCID 86666580, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
150 °C

Procedure

Add (R)-4-chloro-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (0.70 g, 2.78 mmol), 2-(2-(piperidin-4-yl)-4-(2,2,2-trifluoroethyl)-1H-imidazol-1-yl)ethanol dihydrochloride (1.17 g, 1.2 eq), N-methylpyrrolidinone (10 mL) and diisopropylethylamine (2.20 mL, 5.7 eq) in a microwave tube. Seal with crimp cap. Heat in a microwave reactor at 150° C. for one hour. Dilute the reaction mixture with saturated aqueous sodium bicarbonate and extract with ethyl acetate. Dry the organics over anhydrous sodium sulfate, filter, and concentrate in vacuo. Purify by normal phase chromatography, eluting with 5% methanol/dichloromethane to 10% methanol/dichloromethane to 10% 2 M ammonia in methanol/dichloromethane, to give (R)-4-(4-(1-(2-hydroxyethyl)-4-(2,2,2-trifluoroethyl)-1H-imidazol-2-yl)piperidin-1-yl)-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (0.93 g, 68%). MS (ES) m/z=493 [M]+.

Workup

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

Sources & evidence

ORD record
ord-783427df640d412880d497cc69aedbf9
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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