Lithium Hydroxide → HCID 59671517, compound

HRID 70229Notes

Reaction equation

HRID 70229 reaction equation
[OH-].[Li+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][N:13]([C:16]2[O:17][C:18]([C:22]([O:24]CC)=O)=[C:19]([CH3:21])[N:20]=2)[CH:12]([CH2:27][O:28][C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH2:35]([NH2:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C1COCC1.CO.O>[CH2:35]([NH:42][C:22]([C:18]1[O:17][C:16]([N:13]2[CH2:14][CH2:15][N:10]([C:8]([O:7][C:3]([CH3:5])([CH3:4])[CH3:6])=[O:9])[CH2:11][CH:12]2[CH2:27][O:28][C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)=[N:20][C:19]=1[CH3:21])=[O:24])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 7504BenzylamineHCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59671499Ethyl 2-(4-(tert-butoxycarbonyl)-2-((pyridin-3-yloxy)methyl)piperazin-1-yl)-4-methyloxazole-5-carboxylate

Product 1

HCID 59671517HCID 59671517, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide (56 mg, 1.3 mmol) was added to a solution of ethyl 2-(4-(tert-butoxycarbonyl)-2-((pyridin-3-yloxy)methyl)piperazin-1-yl)-4-methyloxazole-5-carboxylate (200 mg, 0.448 mmol) in THF (2 mL), MeOH (2 mL), and water (1 mL). After 3 h, 2.5 mL of the reaction mixture was removed and acidified to pH ˜3 with 1 N aqueous HCl. This was diluted with water (15 mL) and extracted with EtOAc (3×30 mL). The combined extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting yellow oil was dissolved in DMF (3 mL) and benzylamine (0.027 mL, 0.246 mmol), triethylamine (0.094 mL, 0.672 mmol) and TBTU (108 mg, 0.336 mmol) were added. After 14 h, the reaction mixture was concentrated under reduced pressure and purified by HPLC (5 to 95% MeCN/0.1% TFA in H2O/0.1% TFA gradient). This gave the title compound as a brown solid. LC-MS: RT=7.79 min, [M+H]+=508.9.

Workup

  1. custom2.5 mL of the reaction mixture was removed
  2. additionThis was diluted with water (15 mL)
  3. extractionextracted with EtOAc (3×30 mL)
  4. dry with materialThe combined extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe resulting yellow oil was dissolved in DMF (3 mL)
  8. waitAfter 14 h
  9. concentrationthe reaction mixture was concentrated under reduced pressure
  10. custompurified by HPLC (5 to 95% MeCN/0.1% TFA in H2O/0.1% TFA gradient)

Sources & evidence

ORD record
ord-13528711271f4e3c885999f3238adc95
Source dataset
uspto-grants-2014_09
Patent number
US08822472B2

Reaction notes

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