Diisopropylethylamine → (5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-((1S,4S)-5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)-phenyl]amine

HRID 906220Notes

Reaction equation

[Br:1][C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5](Br)=[N:4][CH:3]=1.[CH:12]([N:15]1[CH2:20][C@@H:19]2[CH2:21][C@H:16]1[CH2:17][N:18]2[C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=1)([CH3:14])[CH3:13].CCN(C(C)C)C(C)C>C(O)(C)C>[Br:1][C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5]([NH:28][C:25]2[CH:24]=[CH:23][C:22]([N:18]3[CH2:17][C@@H:16]4[CH2:21][C@H:19]3[CH2:20][N:15]4[CH:12]([CH3:14])[CH3:13])=[CH:27][CH:26]=2)=[N:4][CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

5,8-Dibromo-[1,2,4]triazolo[1,5-a]pyrazine (2.26 g, 8.14 mmol), 4-((1S,4S)-5-Isopropyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-phenylamine (2.07 g, 8.95 mmol, 1.10 equiv.) and DiPEA (4.3 mL, 24.42 mmol, 3.00 equiv.) are mixed in isopropanol (28 mL) under nitrogen. The reaction is heated to 85° C. until completion of the reaction (typically 5 h). The solvent is removed under vacuum and the residue is partitioned between 60 mL aqueous sodium phosphates buffer (pH 7) and 200 mL DCM, the organic layer is washed with 60 mL satd. NaCl, dried on anhydrous Na2SO4, filtered and evaporated in vacuo to yield the title compound (3.67 g) as a green-black foamy solid.

Workup

customThe solvent is removed under vacuum
customthe residue is partitioned between 60 mL aqueous sodium phosphates buffer (pH 7) and 200 mL DCM
washthe organic layer is washed with 60 mL
dry with materialNaCl, dried on anhydrous Na2SO4
filtrationfiltered
customevaporated in vacuo

Sources & evidence

ORD record: ord-9564a2f82cac4df28653f38ca8ce1b90
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012983B2

Reaction notes

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