1,4-Dioxane → HCID 86681495, compound

HRID 340009Notes

Reaction equation

Cl.[NH2:2][C@@H:3]([CH2:16][CH:17]1[CH2:19][CH2:18]1)[CH2:4][N:5]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:15].Br[C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27]C)=O)=[C:23]([CH2:31]Br)[CH:22]=1.C(N(CC)C(C)C)(C)C.O1CCOCC1.[CH3:48][N:49]1[C:53](B2OC(C)(C)C(C)(C)O2)=[CH:52][CH:51]=[N:50]1>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O>[CH:17]1([CH2:16][C@H:3]([N:2]2[CH2:31][C:23]3[C:24](=[CH:29][CH:30]=[C:21]([C:53]4[N:49]([CH3:48])[N:50]=[CH:51][CH:52]=4)[CH:22]=3)[C:25]2=[O:27])[CH2:4][N:5]2[C:6](=[O:15])[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[C:13]2=[O:14])[CH2:19][CH2:18]1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 2-[(2S)-2-amino-3-cyclopropylpropyl]-1H-isoindole-1,3(2H)-dione hydrochloride (257.75 mg, 0.91806 mmol), methyl 4-bromo-2-(bromomethyl)-benzoate (275.80 mg, 0.89555 mmol), N,N-diisopropylethylamine (0.50 mL, 2.9 mmol) and 1,4-dioxane (5.0 mL, 64 mmol) was stirred at 130° C. for 2 hours under microwave irradiation. After the reaction was completed, 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (250.1 mg, 1.202 mmol), bis(tri-t-butylphosphine)palladium (51.1 mg, 0.100 mmol) and water were added. The reaction mixture was stirred at 110° C. for 40 mins under microwave irradiation. Direct purification on prep.HPLC afforded 56 mg (14.2% yield) of the desired final compound. LC-MS found: 441.1 (M+H)+.

Workup

stirringThe reaction mixture was stirred at 110° C. for 40 mins under microwave irradiation
customDirect purification on prep.HPLC

Sources & evidence

ORD record: ord-85e402d546494f059dddea32bbb464e2
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895571B2

Reaction notes

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