HCID 19358398, compound → Indole

Temperature

100 °C

A mixture of 2-iodo-4-(N-(methyl)aminosulphonylmethyl)phenyl aniline (10 g, 30.7 mmol), 1,4-bis-triethylsilyl-3-butyn-1-ol (10.97 g, 36.8 mmol) sodium carbonate (16.26 g, 153.4 mmol) and anhydrous DMF (500 ml) was degassed with N2 for 0.5 h. Pd(OAc)2 (0.7 g, 3.1 mmol) was added and the mixture heated at 100° C. for 6 h. The DMF was removed under vacuum and the residue partitioned between EtOAc (250 ml) and water (250 ml). The solutions were passed through celite to remove insolubles and the aqueous layer separated and extracted further with ethyl acetate (4×200 ml). The combined organics were dried (Na2SO4) and evaporated. The residue was dissolved in methanol (100 ml) and 5N hydrochloric acid (30 ml) was added. The mixture was stirred at room temperature for 2 h and the solvent then removed under vacuum and the residue neutralised with saturated K2CO3 solution. The aqueous was extracted with EtOAc (200 ml) and n-butanol (2×200 ml) and the combined extracts evaporated under vacuum The residue was chromatographed on silica gel eluting with CH2Cl2 /MeOH/NH3 (60:8:1) to give the title-indole (5.39 g, 66%), mp 114-116° C., δ (250 MHz, D6 -DMSO) 2.54 (3H, d, J=4.8Hz, MeNH), 2.83 (2H, t, J=7.5Hz, CH2), 3.60-3.69 (2H, m, CH2 --OH), 4.34 (2H, s, CH2), 4.65 (1H, t, J=5.4Hz, OH), 6.78 (1H, q, J=4.8Hz, MeNH), 7.06 (1H, dd, J=2.2 and 8.3Hz, Ar--H), 7.16 (1H, d, J=2.2Hz, Ar--H), 7.31 (1H, d, J=8.3Hz, Ar--H), 7.51 (1H, s, Ar--H), 10.86 (1H, s, NH).

1. customwas degassed with N2 for 0.5 h
2. customThe DMF was removed under vacuum
3. customthe residue partitioned between EtOAc (250 ml) and water (250 ml)
4. customto remove insolubles
5. customthe aqueous layer separated
6. extractionextracted further with ethyl acetate (4×200 ml)
7. dry with materialThe combined organics were dried (Na2SO4)
8. customevaporated
9. dissolutionThe residue was dissolved in methanol (100 ml)
10. addition5N hydrochloric acid (30 ml) was added
11. customthe solvent then removed under vacuum
12. extractionThe aqueous was extracted with EtOAc (200 ml) and n-butanol (2×200 ml)
13. customthe combined extracts evaporated under vacuum The residue
14. customwas chromatographed on silica gel eluting with CH2Cl2 /MeOH/NH3 (60:8:1)

ORD record

ord-40b3ee3d4deb4eceb6ca90ad21e1a718

Source dataset

uspto-grants-2000_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06025374