N,N-Diethylaniline → 5-Chloro-7-(4-(1-methylpiperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidine

HRID 1853038Notes

Reaction equation

HRID 1853038 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[NH:19][C:18](=O)[N:17]4[CH:21]=[CH:22][N:23]=[C:16]4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.P(Cl)(Cl)([Cl:26])=O.C(N(CC)C1C=CC=CC=1)C.C(=O)(O)[O-].[Na+]>>[Cl:26][C:18]1[N:17]2[CH:21]=[CH:22][N:23]=[C:16]2[CH:15]=[C:14]([C:11]2[CH:12]=[CH:13][C:8]([CH:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[CH:9][CH:10]=2)[N:19]=1

Participants

5

Reactant 4

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 674567377-(4-(1-Methylpiperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidin-5-ol

Product 1

HCID 866853235-Chloro-7-(4-(1-methylpiperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidineYield 71.2%

Conditions

Temperature
50 °C

Procedure

To a suspension of 7-(4-(1-methylpiperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidin-5(6H)-one (0.728 g, 2.361 mmol) in phosphoryl trichloride (12 mL, 131.1 mmol) under nitrogen was added N,N-diethylaniline (0.9390 mL, 5.902 mmol). The reaction was then heated to 50° C. for 4 hours. The reaction was concentrated, and the residue obtained was treated with 15 mL of a 1:1 mixture of ice and saturated aqueous sodium bicarbonate. The resulting mixture was extracted with dichloromethane (4×30 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue obtained was triturated with diethyl ether and the solid was collected by means of vacuum filtration. The solid was saved. The filtrate was concentrated and the resulting residue purified by silica gel column chromatography, eluting with 20% methanol in dichloromethane. The product-containing fractions were concentrated under reduced pressure and the material was combined with the triturated solid to afford 5-chloro-7-(4-(1-methylpiperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidine (550 mg, 1.68 mmol, 63% yield). MS (apci) m/z=327.1 (M+H).

Workup

  1. concentrationThe reaction was concentrated
  2. customthe residue obtained
  3. extractionThe resulting mixture was extracted with dichloromethane (4×30 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue obtained
  8. customwas triturated with diethyl ether
  9. filtrationthe solid was collected by means of vacuum filtration
  10. concentrationThe filtrate was concentrated
  11. customthe resulting residue purified by silica gel column chromatography
  12. washeluting with 20% methanol in dichloromethane
  13. concentrationThe product-containing fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-0308a32cbae6473da9bec45e09003969
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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