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Diisopropylethylamine → tert-Butyl {1-[4-(6,8-dimethyl-3-phenylimidazo[1,2-a]pyrazin-2-yl)phenyl]-cyclobutyl}carbamate

HRID 1774938
Notes
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Reaction equation

HRID 1774938 reaction equation
Br[CH:2]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13][CH2:12]2)=[CH:7][CH:6]=1)=O.[CH3:29][C:30]1[C:31]([NH2:37])=[N:32][CH:33]=[C:34]([CH3:36])[N:35]=1.C(N(C(C)C)CC)(C)C>C(O)(C)C>[CH3:36][C:34]1[N:35]=[C:30]([CH3:29])[C:31]2[N:32]([C:2]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[C:3]([C:5]3[CH:10]=[CH:9][C:8]([C:11]4([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13][CH2:12]4)=[CH:7][CH:6]=3)[N:37]=2)[CH:33]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27747642-Amino-3,5-dimethylpyrazineHCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

Product 1

HCID 89701560tert-Butyl {1-[4-(6,8-dimethyl-3-phenylimidazo[1,2-a]pyrazin-2-yl)phenyl]-cyclobutyl}carbamate

Reagents, catalysts & solvents 1

HCID 3776
Isopropanol
Solvent

Conditions

Temperature
130 °C

Procedure

To a mixture of crude tert-butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate [Int-1-A] (770 mg, 1.61 mmol, 1.0 eq), 3,5-dimethylpyrazin-2-amine (CAS-Nr. 91678-81-8, 218 mg, 1.77 mmol, 1.1 eq) and diisopropylethylamine (0.28 mL, 1.61 mmol, 1.0 eq) in 10 mL isopropanol was added 3 Å molsieves. The reaction mixture was heated to reflux temperature for 2 h. No conversion was observed under these conditions (UPLC-MS). Therefore, the reaction mixture was heated to 130° C. for 1 h under microwave conditions (single mode microwave oven). The reaction mixture was filtered to remove the molsieve and the filtrate was concentrated in vacuo. The crude mixture was purified via MPLC (Biotage Isolera, 25 g Snap cartridge, DCM→DCM/ethanol 95/5) to deliver 249 mg (31%) of the title compound.

Workup

  1. additionwas added 3 Å molsieves
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux temperature for 2 h
  4. filtrationThe reaction mixture was filtered
  5. customto remove the molsieve
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe crude mixture was purified via MPLC (Biotage Isolera, 25 g Snap cartridge, DCM→DCM/ethanol 95/5)

Sources & evidence

ORD record
ord-405d6857334e47ccbe88f85b88ce0264
Source dataset
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09260435B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes