Diisopropylethylamine → 3-oxo-3-[6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.5]non-1-yl]-propionitrile

HRID 1912406Notes

Reaction equation

[NH:1]1[C:4]2([CH2:9][CH2:8][CH2:7][N:6]([C:10]3[C:11]4[CH:18]=[CH:17][NH:16][C:12]=4[N:13]=[CH:14][N:15]=3)[CH2:5]2)[CH2:3][CH2:2]1.CC1N([C:25]([CH2:27][C:28]#[N:29])=[O:26])N=C(C)C=1.C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].[Na+]>O1CCOCC1>[O:26]=[C:25]([N:1]1[C:4]2([CH2:9][CH2:8][CH2:7][N:6]([C:10]3[C:11]4[CH:18]=[CH:17][NH:16][C:12]=4[N:13]=[CH:14][N:15]=3)[CH2:5]2)[CH2:3][CH2:2]1)[CH2:27][C:28]#[N:29]

Participants

Conditions

Temperature: 100 °C

Procedure

An optically-active compound of 4-(1,6-diazaspiro[3.5]non-6-yl)-7H-pyrrolo[2,3-d]pyrimidine (1.55 g) was mixed with 1-cyanoacetyl-3,5-dimethylpyrazole (1.56 g), N,N-diisopropylethylamine (1.66 ml) and 1,4-dioxane (31 ml), and the mixture was heated to 100° C. to stir for 2 hours. The mixture was cooled to room temperature. Then, thereto was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/methanol=20/1 to 9/1) to give the titled compound (1.50 g).

Workup

temperatureThe mixture was cooled to room temperature
extractionthe mixture was extracted with ethyl acetate
washThe organic layer was washed with saturated aqueous sodium chloride solution
concentrationconcentrated under reduced pressure
customThe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/methanol=20/1 to 9/1)

Sources & evidence

ORD record: ord-58f2e54c222243958a8c7da694e55089
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08609647B2

Reaction notes

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