Sodium Bicarbonate → 2-{1-[4-(2-Methyl-6-phenyl-imidazo[1,2-a]pyrimidin-7-yl)benzyl]-piperidine-4-yl}-quinoxaline

HRID 1851285Notes

Reaction equation

HRID 1851285 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:16]=[N:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH2:3][CH2:2]1.[CH3:17][C:18]1[N:19]=[C:20]2[N:25]=[C:24]([C:26]3[CH:33]=[CH:32][C:29]([CH:30]=O)=[CH:28][CH:27]=3)[C:23]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[CH:22][N:21]2[CH:40]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>CN1C(=O)CCC1.C(O)(=O)C.C(N(CC)CC)C>[CH3:17][C:18]1[N:19]=[C:20]2[N:25]=[C:24]([C:26]3[CH:27]=[CH:28][C:29]([CH2:30][N:1]4[CH2:2][CH2:3][CH:4]([C:7]5[CH:16]=[N:15][C:14]6[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=6)[N:8]=5)[CH2:5][CH2:6]4)=[CH:32][CH:33]=3)[C:23]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)=[CH:22][N:21]2[CH:40]=1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 211980262-(Piperidin-4-yl)quinoxalineHCID 867030344-(2-Methyl-6-phenyl-imidazo[1,2-a]pyrimidin-7-yl)benzaldehyde

Product 1

HCID 687510252-{1-[4-(2-Methyl-6-phenyl-imidazo[1,2-a]pyrimidin-7-yl)benzyl]-piperidine-4-yl}-quinoxaline

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 8471TriethylamineSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

219.2 mg (0.76 mmol) 2-Piperidine-4-ylquinoxaline are dissolved in 5.5 mL NMP. After addition of 0.2 mL triethylamine the reaction mixture is stirred for one hour. 200 mg (0.64 mmol) 4-(2-Methyl-6-phenyl-imidazo[1,2-a]pyrimidin-7-yl)benzaldehyde and 0.06 mL acetic acid are added. The reaction mixture is stirred overnight at room temperature. 148 mg (0.7 mmol) NaBH(OAc)3, are added in portions and the reaction mixture is stirred at room temperature for 18 hours. Additionally 75 mg NaBH(OAc)3 and 0.03 mL acetic acid are added and the stirring is continued for four days. The reaction mixture is treated with saturated NaHCO3 and vigorously stirred for one hour. The precipitate is filtered off, washed with water and dried. This solid is treated three times with each 20 mL dichloromethane. After filtration of the combined dichloromethane extracts the filtrate is evaporated and the residue purified by chromatography on silica gel (dichloromethane/methanol). After an additional purification by HPLC 84 mg (25.8%) of the pure product are obtained.

Workup

  1. stirringThe reaction mixture is stirred overnight at room temperature
  2. stirringthe reaction mixture is stirred at room temperature for 18 hours
  3. waitthe stirring is continued for four days
  4. stirringvigorously stirred for one hour
  5. filtrationThe precipitate is filtered off
  6. washwashed with water
  7. customdried
  8. additionThis solid is treated three times with each 20 mL dichloromethane
  9. filtrationAfter filtration of the combined dichloromethane
  10. customis evaporated
  11. customthe residue purified by chromatography on silica gel (dichloromethane/methanol)
  12. customAfter an additional purification by HPLC 84 mg (25.8%) of the pure product
  13. customare obtained

Sources & evidence

ORD record
ord-53265d67b7f94b3494bee656be7af6ec
Source dataset
uspto-grants-2015_02
Patent number
US08957064B2

Reaction notes

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