Tert-butyl acetoacetate → 2-Benzoyl-6-chloro-3-(3-oxobutyrylamino)indole

HRID 379861Notes

Reaction equation

[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:12](=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:20](OC(C)(C)C)(=[O:25])[CH2:21][C:22]([CH3:24])=[O:23].C(OCC)(=O)C.CCCCCC>C1(C)C(C)=CC=CC=1>[C:12]([C:3]1[NH:4][C:5]2[C:10]([C:2]=1[NH:1][C:20](=[O:25])[CH2:21][C:22](=[O:23])[CH3:24])=[CH:9][CH:8]=[C:7]([Cl:11])[CH:6]=2)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 3-amino-2-benzoyl-6-chloroindole (Example 1) (850 mg, 4.07 mmol) and tert-butyl acetoacetate (1.3 ml, 8.15 mmol) in xylene (10 ml) was heated at 120° C. for 5 h. The mixture was concentrated and purified by flash column chromatography eluting with hexane/ethyl acetate (2/1) to give a yellow amorphous solid. Recrysalization from ethyl acetate/hexane afforded 450 mg (31%) of the titled compound as a pale yellow solid. m.p.: 170-173° C. 1H-NMR (CDCl3) δ: 10.22 (1H, br s), 8.47 (1H, br s), 8.01 (1H, d, J=8.8 Hz), 7.83-7.77 (2H, m), 7.65-7.50 (3H, m), 7.32 (1H, d, J=1.5 Hz), 7.11 (1H, dd, J=1.5, 8.8 Hz), 3.56 (2H, s), 2.32 (3H, s).

Workup

concentrationThe mixture was concentrated
custompurified by flash column chromatography
washeluting with hexane/ethyl acetate (2/1)
customto give a yellow amorphous solid

Sources & evidence

ORD record: ord-b015cea3acd648a0bff677eb523c6955
Source dataset: uspto-grants-2001_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06300363B1

Reaction notes

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