Water → HCID 21110936, compound

HRID 1627545Notes

Reaction equation

HRID 1627545 reaction equation
C(OC([N:8]1[C@@H:13]([CH3:14])[CH2:12][N:11]([C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:23]=[N:24][C:25]([NH2:29])=[C:26]([OH:28])[CH:27]=3)=[CH:18][CH:17]=2)[CH2:10][C@H:9]1[CH3:31])=O)(C)(C)C.Br[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[CH3:40].C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[NH2:29][C:25]1[N:24]=[CH:23][C:22]([C:19]2[CH:20]=[CH:21][C:16]([C:15]([N:11]3[CH2:10][CH:9]([CH3:31])[NH:8][CH:13]([CH3:14])[CH2:12]3)=[O:30])=[CH:17][CH:18]=2)=[CH:27][C:26]=1[O:28][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[CH3:40]

Participants

6

Reactant 4

HCID 962WaterHCID 6992o-Xylyl bromideHCID 10796Cesium carbonateHCID 58885805HCID 58885805, compound

Product 1

HCID 21110936HCID 21110936, compoundYield 47.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of (2R,6S)-4-[4-(6-Amino-5-hydroxy-pyridin-3-yl)-benzoyl]-2,6-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (100 mg, 0.23 mmol) and 1-bromomethyl-2-methyl-benzene (47 mg, 0.25 mmol) in DMF (2 mL) was added 2 M Cs2CO3 (0.35 mL, 0.7 mmol) followed by water (0.5 mL). The mixture was stirred at room temperature overnight. LCMS showed the reaction was completed, DMF was removed, followed by addition of 4 N HCl in dioxane (2 mL) and the reaction was stirred at room temperature for 3 hr. The volatiles were removed followed by addition of methanol. This solution was purified by prep-HPLC to afford {4-[6-Amino-5-(2-methyl-benzyloxy)-pyridin-3-yl]-phenyl}-(3,5-dimethyl-piperazin-1-yl)-methanone (47 mg, yield 46.6%).

Workup

  1. customDMF was removed
  2. additionfollowed by addition of 4 N HCl in dioxane (2 mL)
  3. stirringthe reaction was stirred at room temperature for 3 hr
  4. customThe volatiles were removed
  5. additionfollowed by addition of methanol
  6. customThis solution was purified by prep-HPLC

Sources & evidence

ORD record
ord-981f359d30d14cc6a1c748910d974957
Source dataset
uspto-grants-2014_07
Patent number
US08785632B2

Reaction notes

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