1,2-Dichloroethane → HCID 136052169, compound

HRID 884637Notes

Reaction equation

HRID 884637 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:13][C:12](=[O:14])[N:11]=[C:10]([C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([CH3:22])[CH:16]=3)[CH:9]=2)=[C:4]([CH3:23])[CH:3]=1.ClCCCl.C([N:35]1[CH2:40][CH2:39][CH:38]([CH:41]=O)[CH2:37][CH2:36]1)(OC(C)(C)C)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[OH:21][C:18]1[CH:19]=[CH:20][C:15]([C:10]2[CH:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][CH2:41][CH:38]4[CH2:39][CH2:40][NH:35][CH2:36][CH2:37]4)=[CH:3][C:4]=3[CH3:23])[NH:13][C:12](=[O:14])[N:11]=2)=[CH:16][C:17]=1[CH3:22]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 136348330HCID 136348330, compound

Product 1

HCID 136052169HCID 136052169, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

In a round bottom flask was added 6-(4-amino-2-methylphenyl)-4-(4-hydroxy-3-methylphenyl)pyrimidin-2(1H)-one (3) (30 mg, 0.10 mmol), 1,2 dichloroethane (2.0 mL), acetic acid (0.1 mL), and commercially available N-Boc-4-formyl piperidine (29 uL, 0.14 mmol). The reaction was stirred at room temperature for 15 minutes before adding sodium triacetoxy borohydride (30 mg, 0.14 mmol). Stirring was continued at room temperature overnight. The reaction was then quenched with saturated NaHCO3, extracted with EtOAc, dried over Na2SO4 and concentrated to dryness. The resultant oil was then dissolved in 4N HCl/dioxane (1.0 mL) and allowed to sit at RT for 30 min. or until Boc deprotection was complete. The 4N HCl/dioxane was decanted, and the residual solid product was rinsed with EtOAc 4×. The resulting orange solid was then dissolved in MeOH and purified by preparatory HPLC (5-85% gradient of AmAc/ACN, 15 min.) to give the product 4-(4-hydroxy-3-methylphenyl)-6-{2-methyl-4-[(piperidin-4 ylmethyl)amino]phenyl}pyrimidin-2(1H)-one as the acetate salt after lyopholyzation (24 mg, 59% yield).

Workup

  1. stirringStirring
  2. waitwas continued at room temperature overnight
  3. customThe reaction was then quenched with saturated NaHCO3
  4. extractionextracted with EtOAc
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness
  7. dissolutionThe resultant oil was then dissolved in 4N HCl/dioxane (1.0 mL)
  8. waitto sit at RT for 30 min. or until Boc deprotection
  9. customThe 4N HCl/dioxane was decanted
  10. washthe residual solid product was rinsed with EtOAc 4×
  11. dissolutionThe resulting orange solid was then dissolved in MeOH
  12. custompurified by preparatory HPLC (5-85% gradient of AmAc/ACN, 15 min.)

Sources & evidence

ORD record
ord-8e30a45119784808872d613d26f1acfa
Source dataset
uspto-grants-2012_08
Patent number
US08242129B2

Reaction notes

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