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

HRID 1270868Notes

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]>CN(C=O)C.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 DMF (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). 1HNMR (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-51b6d82b53814315a2c7c18b769b1081
Source dataset: uspto-grants-2007_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07202363B2

Reaction notes

Loading…