Potassium Carbonate → Tert-butyl 4-(2-bromothieno[3,2-c]pyridin-4-yl)piperazine-1-carboxylate

HRID 549290Notes

Reaction equation

[Br:1][C:2]1[S:10][C:9]2[CH:8]=[CH:7][N:6]=[C:5](Cl)[C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[N:18]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1>CS(C)=O>[Br:1][C:2]1[S:10][C:9]2[CH:8]=[CH:7][N:6]=[C:5]([N:21]3[CH2:20][CH2:19][N:18]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23][CH2:22]3)[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

2-Bromo-4-chlorothieno[3,2-c]pyridine (5.0 g, 20.24 mmol) and K2CO3 (13.97 g, 101.2 mmol) was stirred in DMSO (20 mL) followed by addition of tert-butyl piperazine-1-carboxylate (4.14 g, 22.26 mmol). The reaction mixture was stirred at 100° C. for 6 days. The reaction mixture was filtered to eliminate the carbonate and addition of water (50 mL) and ethyl was followed. The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried (MgSO4) and the solvent was evaporated. The crude product was purified by flash chromatography using ethyl acetate/hexanes (2/8) as eluent to give 2 g of the desired product, yield 25%, 99% pure. 1H NMR (270 MHz, CDCl3) δ 1.48 (s, 9H), 1.52-1.63 (m, 1H), 3.42-3.47 (m, 4H), 3.61-3.64 (m, 4H), 7.22 (dd, J=5.4, 1 Hz, 1H), 7.35 (d, J=1 Hz, 1H), 8.04 (d, J=5.4 Hz, 1H). m/z=398.91 (M+H), bromide pattern.

Workup

filtrationThe reaction mixture was filtered
additionthe carbonate and addition of water (50 mL) and ethyl
customThe phases were separated
extractionthe aqueous phase was extracted with ethyl acetate
dry with materialThe combined organic phases were dried (MgSO4)
customthe solvent was evaporated
customThe crude product was purified by flash chromatography

Sources & evidence

ORD record: ord-f16eb97eb10f433d8398366f8bce1c3e
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07943639B2

Reaction notes

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