N,N-Dimethylglycine → HCID 56597424, compound

HRID 2036201Notes

Reaction equation

HRID 2036201 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2Br)[CH:12]1[C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[O:29][CH2:30][C:31]([O:33]CC)=[O:32])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:36][S:37]([NH2:40])(=[O:39])=[O:38].CN(C)CC(O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[Cu]I>[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[NH:40][S:37]([CH3:36])(=[O:39])=[O:38])[CH:12]1[C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[O:29][CH2:30][C:31]([OH:33])=[O:32])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 62657Potassium Phosphate, TribasicHCID 72879MethanesulfonamideHCID 66653872HCID 66653872, compound

Product 1

HCID 56597424HCID 56597424, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture under Ar of (±)-5-bromo-1-(2-ethoxycarbonylmethoxy-5-fluoro-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (108 mg, 0.20 mmol, 1.00 eq.), methanesulfonamide (23 mg, 0.24 mmol, 1.20 eq.), N,N-dimethylglycine (4.3 mg, 0.04 mmol, 0.2 eq.), potassium phosphate tribasic (106 mg, 0.50 mmol, 2.5 eq.), and copper (I) iodide (7.6 mg, 0.04 mmol, 0.2 eq.) in DMF (2 mL) was stirred at 150° C. for 48 hours. The mixture was allowed to cool to r.t. and partitioned between AcOEt (25 mL) and H2O (25 mL). The layers were separated and the aq. phase was extracted with AcOEt (2×25 mL). The comb. org. phases were dried over MgSO4 and concentrated in vacuo. The residue was dissolved in DMF (1.0 mL). 1M aq. NaOH soln. (1.0 mL) was added. The mixture was stirred at r.t. for 18 hours. The solution was neutralized with 1M aq. HCl soln. (1.0 mL), then purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 uM, acidic conditions, detection: UV/MS) to give the desired acid.

Workup

  1. custompartitioned between AcOEt (25 mL) and H2O (25 mL)
  2. customThe layers were separated
  3. extractionthe aq. phase was extracted with AcOEt (2×25 mL)
  4. dry with materialphases were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in DMF (1.0 mL)
  7. addition(1.0 mL) was added
  8. custom(1.0 mL), then purified by prep

Sources & evidence

ORD record
ord-ea76df8bb2ae429ea27dacec9326d494
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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