Diisopropylethylamine → (S)-2-(1-((6-Amino-5-cyanopyrimidin-4-yl)amino)-3-(benzyloxy)propyl)-3-(3,5-difluorophenyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazine-5-carbonitrile

HRID 1052664Notes

Reaction equation

[NH2:1][C@H:2]([C:13]1[N:18]([C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=2)[C:17](=[O:27])[C:16]2=[C:28]([C:31]#[N:32])[CH:29]=[CH:30][N:15]2[N:14]=1)[CH2:3][CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[NH2:33][C:34]1[C:39]([C:40]#[N:41])=[C:38](Cl)[N:37]=[CH:36][N:35]=1.C(N(CC)C(C)C)(C)C>C(O)CCC>[NH2:33][C:34]1[N:35]=[CH:36][N:37]=[C:38]([NH:1][C@H:2]([C:13]2[N:18]([C:19]3[CH:20]=[C:21]([F:26])[CH:22]=[C:23]([F:25])[CH:24]=3)[C:17](=[O:27])[C:16]3=[C:28]([C:31]#[N:32])[CH:29]=[CH:30][N:15]3[N:14]=2)[CH2:3][CH2:4][O:5][CH2:6][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:39]=1[C:40]#[N:41]

Participants

Conditions

Temperature: 120 °C

Procedure

In a reactor vessel (S)-2-(1-amino-3-(benzyloxy)propyl)-3-(3,5-difluorophenyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazine-5-carbonitrile (42 mg, 0.1 mmol) and 4-amino-6-chloropyrimidine-5-carbonitrile (16 mg, 0.1 mmol) were dissolved in 1-butanol (840 μl) under argon atmosphere. N,N-Diisopropylethylamine (76 μl, 0.87 mmol) was added and the reaction mixture was heated at 120° C. overnight. Further N,N-diisopropylethylamine (76 μl, 0.87 mmol) was added afterwards and the reaction mixture was stirred at 120° C. overnight. The crude was evaporated and purified using SP1® Purification System (0% to 100%, hexane-ethyl acetate) to obtain 34 mg (64% yield) of the title compound as a yellow solid. Purity 97%.

Workup

customThe crude was evaporated
custompurified
customSP1® Purification System (0% to 100%, hexane-ethyl acetate)

Sources & evidence

ORD record: ord-d14207ba7c864487957ef67c744c8f2c
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09388189B2

Reaction notes

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