Triethylamine → 7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-carboxylic acid tert-butyl ester

HRID 589948Notes

Reaction equation

Cl[C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.CCN(CC)CC.[C:18]([O:22][C:23]([N:25]1[CH2:32][CH2:31][NH:30][CH2:29][C:26]21[CH2:28][CH2:27]2)=[O:24])([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C>[C:18]([O:22][C:23]([N:25]1[CH2:32][CH2:31][N:30]([C:2]2[C:3]3[CH:10]=[CH:9][NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:29][C:26]21[CH2:27][CH2:28]2)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

Conditions

Temperature: 110 °C

Procedure

To commercially available 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (1.0 g, 6.5 mmol) dissolved in DMF (5 ml) was added Et3N (1.3 ml, 9.8 mmol) followed by commercially available 4,7-diaza-spiro[2.5]octane-4-carboxylic acid tert-butyl ester (1.5 g, 7.2 mmol). The reaction mixture was heated for 16 hours at 110° C. After evaporation of the solvent in vacuo the crude mixture was treated with water (25 mL) and extracted with EtOAc (4×30 mL) the combined organic phases were washed with brine (2×20 mL), dried over Na2SO4, filtered and concentrated in vacuo to provide 1.5 g crude. The product was purified by flash chromatography on silica using EtOAc in heptane as eluent.

Workup

customAfter evaporation of the solvent in vacuo the crude mixture
additionwas treated with water (25 mL)
extractionextracted with EtOAc (4×30 mL) the combined organic phases
washwere washed with brine (2×20 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customto provide 1.5 g crude
customThe product was purified by flash chromatography on silica

Sources & evidence

ORD record: ord-f52b87c345ab4d73b1981bbf92fc0fa2
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09233964B2

Reaction notes

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