Diisopropylethylamine → 6-bromo-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)-3-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)phenyl)imidazo[1,2-a]pyrazin-8-amine

HRID 928692Notes

Reaction equation

HRID 928692 reaction equation
[O:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]([C:11]3[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][C:12]=3[O:18][CH2:19][CH2:20][O:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[CH2:7][CH2:6]2)[CH2:2]1.[Br:28][C:29]1[N:30]=[C:31](Br)[C:32]2[N:33]([CH:35]=[CH:36][N:37]=2)[CH:34]=1.C(N(CC)C(C)C)(C)C.C([O-])(O)=O.[Na+]>CC(O)C.C(Cl)Cl>[Br:28][C:29]1[N:30]=[C:31]([NH:15][C:14]2[CH:16]=[CH:17][C:11]([N:8]3[CH2:9][CH2:10][N:5]([CH:3]4[CH2:2][O:1][CH2:4]4)[CH2:6][CH2:7]3)=[C:12]([O:18][CH2:19][CH2:20][O:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[CH:13]=2)[C:32]2[N:33]([CH:35]=[CH:36][N:37]=2)[CH:34]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 150258436,8-Dibromoimidazo[1,2-a]pyrazineHCID 1181879194-(4-(oxetan-3-yl)piperazin-1-yl)-3-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)aniline

Product 1

HCID 1181879216-bromo-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)-3-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)phenyl)imidazo[1,2-a]pyrazin-8-amine

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 4-(4-(oxetan-3-yl)piperazin-1-yl)-3-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)aniline XXIV (619 mg, 2.17 mmol) and 6,8-dibromoimidazo[1,2-a]pyrazine (601 mg, 2.2 mmol) in IPA (15 mL) was added N,N-Diisopropylethylamine (0.95 ml, 5.43 mmol). The mixture was stirred at 110° C. for 16 h. After this time, DCM (10 mL) and sat aqueous NaHCO3 (15 mL) were added. The aqueous layer was separated and extracted with DCM (2×10 mL). The combined organic extracts were washed with brine (10 mL) and dried over sodium sulfate. The resulting residue was purified by column chromatography ISCO Rf (24 g column) eluting with a gradient of 100% DCM—60:35:5 DCM:Et2O:MeOH to provide 6-bromo-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)-3-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)phenyl)imidazo[1,2-a]pyrazin-8-amine XXV.

Workup

  1. additionwere added
  2. customThe aqueous layer was separated
  3. extractionextracted with DCM (2×10 mL)
  4. washThe combined organic extracts were washed with brine (10 mL)
  5. dry with materialdried over sodium sulfate
  6. customThe resulting residue was purified by column chromatography ISCO Rf (24 g column)
  7. washeluting with a gradient of 100% DCM—60:35:5 DCM

Sources & evidence

ORD record
ord-eaa48ad21a0d49e9a427966310a4d04e
Source dataset
uspto-grants-2016_03
Patent number
US09290505B2

Reaction notes

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