Diisopropylethylamine → (R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 1034883Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.[Cl:15][C:16]1[C:17](F)=[C:18]2[C:24]([NH2:25])=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1.C(N(C(C)C)C(C)C)C>CN1C(=O)CCC1>[NH2:25][C:24]1[C:18]2[C:19](=[N:20][CH:21]=[C:16]([Cl:15])[C:17]=2[N:1]2[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]2)[NH:22][CH:23]=1

Participants

Conditions

Temperature: 120 °C

Procedure

(R)-tert-Butyl piperidin-3-ylcarbamate (1619 mg, 8.08 mmol) was added to a mixture of 5-chloro-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (500 mg, 2.69 mmol; Example 8, Step D) and N-ethyl-N-isopropylpropan-2-amine (1408 μL, 8.08 mmol) in NMP (6.75 mL). N2 was bubbled through the mixture for 5 minutes, and the reaction was stirred at 120° C. under N2 for 24 hours. The mixture was allowed to cool, was diluted with 20% EtOAc/Et2O (200 mL) and washed with water (5×50 mL). The organic layer was then dried over MgSO4, filtered, and concentrated in vacuo to provide the crude (R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate. LCMS (APCI+) m/z 366 (M+H)+.

Workup

customN2 was bubbled through the mixture for 5 minutes
temperatureto cool
additionwas diluted with 20% EtOAc/Et2O (200 mL)
washwashed with water (5×50 mL)
dry with materialThe organic layer was then dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-90ea01812cee407a98dc6ec7758092a5
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08545897B2

Reaction notes

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