Diisopropylethylamine → 5-Chloro-2-{[1-(5-fluoropyrimidin-2-yl)ethyl]amino}-6-[(5-methyl-1H-pyrazol-3-yl)amino]nicotinonitrile

HRID 75916Notes

Reaction equation

C1(C2NN=C(N[C:10]3[N:15]=[C:14]([NH:16][C@H:17](C4C=CC(F)=CC=4)C)[C:13]([CH2:26]NC(=O)CN4CCOCC4)=C[C:11]=3[F:37])C=2)CC1.Cl[C:39]1[N:46]=[C:45]([NH:47][C:48]2[CH:52]=[C:51]([CH3:53])[NH:50][N:49]=2)[C:44]([Cl:54])=[CH:43][C:40]=1[C:41]#[N:42].CC[N:57](C(C)C)C(C)C>CCCCO>[Cl:54][C:44]1[C:45]([NH:47][C:48]2[CH:52]=[C:51]([CH3:53])[NH:50][N:49]=2)=[N:46][C:39]([NH:57][CH:13]([C:14]2[N:15]=[CH:10][C:11]([F:37])=[CH:17][N:16]=2)[CH3:26])=[C:40]([CH:43]=1)[C:41]#[N:42]

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of 1-(5-fluoropyrimidin-2-yl)ethanamine (Method 72, 0.05 g, 0.35 mmol), 2,5-dichloro-6-[(5-methyl-1H-pyrazol-3-yl)amino]nicotinonitrile (Method 60, 0.06 g, 0.25 mmol), and DIEA (0.12 ml, 0.7 mmol) in n-BuOH (10 ml) was charged into a microwave reaction vessel. The vessel was sealed and heated in microwave reactor at 160° C. for 6 hours. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography (DCM-EtOAc=1:1) to give the title compound as a yellow solid (0.017 g, 15%). LC-MS, 373 (M+1). 1H NMR (400 MHz, MeOD) δ 8.75 (s, 2H), 7.45 (s, 1H), 6.40 (s, 1H), 5.45 (br 1H), 2.35 (s, 3H), 1.60 (d, 3H).

Workup

additionwas charged into a microwave reaction vessel
customThe vessel was sealed
customThe solvent was removed under reduced pressure
customthe residue was purified by silica gel chromatography (DCM-EtOAc=1:1)

Sources & evidence

ORD record: ord-a4c729850559471d9ce44ef84666204d
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835465B2

Reaction notes

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