Sodium Carbonate → Tert-butyl (2e)-3-(4-amino-3-bromothieno[3,2-c]pyridin-7-yl)acrylate

HRID 2390640Notes

Reaction equation

[Br:1][C:2]1[C:6]2[C:7]([NH2:12])=[N:8][CH:9]=[C:10](I)[C:5]=2[S:4][CH:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Na+].[Na+].[C:38]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])(=[O:41])[CH:39]=[CH2:40]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:12][C:7]1[C:6]2[C:2]([Br:1])=[CH:3][S:4][C:5]=2[C:10](/[CH:40]=[CH:39]/[C:38]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])=[CH:9][N:8]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of Example 21A (2.50 g, 7.04 mmol), PPh3 (0.370 g, 1.41 mmol), and Na2CO3 (1.49 g, 14.1 mmol) in DME (35 mL) was treated with tert-butyl acrylate (2.00 mL, 14.1 mmol) and palladium(II) acetate (0.158 g, 0.704 mmol). The reaction was heated to 80° C. under an atmosphere of nitrogen for 16 hours. The reaction was cooled to ambient temperature and partitioned between ethyl acetate (100 mL) and brine. The organic phase was washed with brine (2×100 mL), dried (Na2SO4), filtered, and concentrated. The compound was purified by flash chromatography on silica gel using heptane/ethyl acetate (6:1) to (3:1) to provide the desired product (1.70 g, 3.01 mmol). 1H NMR (DMSO-d6, 400 MHz) δ 8.24 (s, 1H), 7.94 (s, 1H), 7.62 (d, 1H), 7.17 (br s, 2H), 6.22 (d, 1H), 1.48 (s, 9H); MS m/e 355/357 (M+H)+.

Workup

temperatureThe reaction was cooled to ambient temperature
custompartitioned between ethyl acetate (100 mL) and brine
washThe organic phase was washed with brine (2×100 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe compound was purified by flash chromatography on silica gel

Sources & evidence

ORD record: ord-ab01f1d607814de6a63ebba4ce8a3efc
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08273736B2

Reaction notes

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