Triethylamine → 6-[1-[(3-hydroxy-4-methoxyphenyl)methyl]piperidin-4-yl]-2-piperidin-1-yl-1H-pyrimidin-4-one

HRID 1526475Notes

Reaction equation

HRID 1526475 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]3)[N:11]=[C:10]([OH:20])[CH:9]=2)[CH2:4][CH2:3]1.[OH:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[CH:25]=O.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.ClCCl>[OH:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[CH2:25][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[N:13]=[C:12]([N:14]3[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]3)[N:11]=[C:10]([OH:20])[CH:9]=2)[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 12127IsovanillinHCID 5049666Sodium triacetoxyborohydrideHCID 178479621HCID 178479621, compound

Product 1

HCID 1784907796-[1-[(3-hydroxy-4-methoxyphenyl)methyl]piperidin-4-yl]-2-piperidin-1-yl-1H-pyrimidin-4-oneYield 68%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-Piperidin-4-yl-2-piperidin-1-yl-pyrimidin-4-ol, hydrochloride salt (2.0 mmol), 3-hydroxy-4-methoxy-benzaldehyde (2.6 mmol), triethylamine (4.0 mmol) and 3 drops of acetic acid in dry dichloromethane (20 mL) was stirred at room temperature for 3 hours. Then sodium triacetoxyborohydride (6.0 mmol) was added in portions and stirring was continued for 48 hours (monitored by TLC). The mixture was quenched with saturated aqueous sodium bicarbonate solution (20 mL), and the product was extracted with dichloromethane (2×10 mL). The extracts were washed with brine and dried over sodium sulfate. The solvent was evaporated in vacuo to give a crude product. Purification via column chromatography (silica gel, ethyl acetate/hexane) afforded 6-[1-(3-hydroxy-4-methoxy-benzyl)-piperidin-4-yl]-2-piperidin-1-yl-pyrimidin-4-ol (Compound IIb, 542 mg, 68%).

Workup

  1. stirringstirring
  2. waitwas continued for 48 hours
  3. customThe mixture was quenched with saturated aqueous sodium bicarbonate solution (20 mL)
  4. extractionthe product was extracted with dichloromethane (2×10 mL)
  5. washThe extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was evaporated in vacuo
  8. customto give a crude product
  9. customPurification via column chromatography (silica gel, ethyl acetate/hexane)

Sources & evidence

ORD record
ord-50256424b15f425ea82835846738be1a
Source dataset
uspto-grants-2015_07
Patent number
US09085585B2

Reaction notes

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