Dimethylamine → (5-Bromo-imidazo[1,2-a]pyrazin-8-yl)-(3-dimethylaminomethyl-4-morpholin-4-yl-phenyl)-carbamic acid tert-butyl ester

HRID 1366225Notes

Reaction equation

HRID 1366225 reaction equation
[Br:1][C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[C:5]([N:11]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:12]2[CH:13]=[CH:14][C:15]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[C:16]([CH:23]=2)[CH2:17]OS(C)(=O)=O)=[N:4][CH:3]=1.[CH3:37][NH:38][CH3:39].C([O-])([O-])=O.[K+].[K+]>C1COCC1>[NH3:4].[C:33]([O:32][C:30](=[O:31])[N:11]([C:5]1[C:6]2[N:7]([CH:8]=[CH:9][N:10]=2)[C:2]([Br:1])=[CH:3][N:4]=1)[C:12]1[CH:13]=[CH:14][C:15]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)=[C:16]([CH2:17][N:38]([CH3:39])[CH3:37])[CH:23]=1)([CH3:35])([CH3:34])[CH3:36]

Participants

6

Reactant 3

HCID 674DimethylamineHCID 11430Potassium CarbonateHCID 86652630Methanesulfonic acid 5-[(5-bromo-imidazo[1,2-a]pyrazin-8-yl)-tert-butoxycarbonyl-amino]-2-morpholin-4-yl-benzyl ester

Product 2

HCID 222AmmoniaHCID 86652631(5-Bromo-imidazo[1,2-a]pyrazin-8-yl)-(3-dimethylaminomethyl-4-morpholin-4-yl-phenyl)-carbamic acid tert-butyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
75 °C

Procedure

To a solution of methanesulfonic acid 5-[(5-bromo-imidazo[1,2-a]pyrazin-8-yl)-tert-butoxycarbonyl-amino]-2-morpholin-4-yl-benzyl ester (0.098 g, 0.169 mmol) in THF (0.5 mL) is added 2M N,N-dimethylamine solution in THF (0.50 mL, 1.1 mmol) followed by K2CO3 (0.028 g, 0.202 mmol). The reaction mixture is stirred at room temperature for 1.5 hours and at 75° C. for an additional 3 hours. The solvent is removed under vacuum and the residue is partitioned between ethyl acetate and water. The organic layer is dried over MgSO4, filtered and concentrated in vacuo to give the crude compound which is purified by silica gel column chromatography. Elution using 97:3 DCM:NH3 (7M in MeOH) affords the title compound (0.0543 g, 61%). LCMS: Rt 2.37 min (95%), m/z (ES+) 531/533 (M+H)+.

Workup

  1. customThe solvent is removed under vacuum
  2. customthe residue is partitioned between ethyl acetate and water
  3. dry with materialThe organic layer is dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give the crude compound which
  7. customis purified by silica gel column chromatography
  8. washElution

Sources & evidence

ORD record
ord-ad74bbcd91fe45c48ca511293daa9486
Source dataset
uspto-grants-2011_02
Patent number
US07893058B2

Reaction notes

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