Diisopropylethylamine → tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

HRID 1774943Notes

Reaction equation

HRID 1774943 reaction equation
[Br:1][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:4].[NH2:29][C:30]1[N:31]=[CH:32][C:33]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[N:34][CH:35]=1.C(N(C(C)C)CC)(C)C>C(#N)CCC>[Br:1][CH:2]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:3]([C:5]1[CH:6]=[CH:7][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:9][CH:10]=1)=[O:4].[C:18]([O:17][C:16]([NH:15][C:11]1([C:8]2[CH:7]=[CH:6][C:5]([C:3]3[N:29]=[C:30]4[CH:35]=[N:34][C:33]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:32][N:31]4[C:2]=3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:10][CH:9]=2)[CH2:14][CH2:13][CH2:12]1)=[O:22])([CH3:20])([CH3:19])[CH3:21]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 22271413Ethyl 5-Aminopyrazine-2-carboxylateHCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

Product 2

HCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamateHCID 89691425Ethyl 2-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-3-phenylimidazo[1,2-a]pyrazine-6-carboxylate

Reagents, catalysts & solvents 1

HCID 8008ButyronitrileSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of crude tert-butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate [Int-1-A] (213 mg, 0.38 mmol, 1.0 eq), ethyl 5-aminopyrazine-2-carboxylate (CAS-Nr. 54013-06-8, 70.5 mg, 0.42 mmol, 1.1 eq.) and diisopropylethylamine (0.055 mL, 0.42 mmol, 1.1 eq) in 2.3 mL butyronitrile was added predried 3 Å mol sieves. The mixture was heated overnight at 120° C. The reaction mixture was partitioned between DCM/water and was filtered through a phase separator. The remaining volatile organic components were removed by the use of a rotary evaporator. In parallel we conducted the same experiment in the absence of diisopropylethylamine following the same protocol. The crude materials of both experiments were combined and purified via MPLC (Biotage Isolera, 25 g Snap-cartridge; eluent: hexane/ethyl acetate (1/1)→ethyl acetate) to deliver 69 mg (14%, yield based on combined amount of tert-butyl (1-{4-[bromo(phenyl)acetyl]-phenyl}cyclobutyl)carbamate) of the title compound.

Workup

  1. additionwas added
  2. customThe reaction mixture was partitioned between DCM/water
  3. filtrationwas filtered through a phase separator
  4. customThe remaining volatile organic components were removed by the use of a rotary evaporator
  5. custompurified via MPLC (Biotage Isolera, 25 g Snap-cartridge; eluent: hexane/ethyl acetate (1/1)→ethyl acetate)

Sources & evidence

ORD record
ord-9c127fc3192e41b290bc6e63be7810f1
Source dataset
uspto-grants-2016_02
Patent number
US09260435B2

Reaction notes

Loading…