Diisopropylethylamine → HCID 131726839, compound

HRID 901998Notes

Reaction equation

HRID 901998 reaction equation
[NH2:1][C@@H:2]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C@H:3]1[O:12][CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].[Cl:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][C:26]([C:31](O)=[O:32])=[CH:25]2.Cl.C(N=C=N)C.ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>O1CCCC1.C(OCC)(=O)C>[C:17]([O:16][C:14](=[O:15])[CH2:13][O:12][C@H:3]1[C@H:2]([NH:1][C:31]([C:26]2[NH:27][C:28]3[C:24]([CH:25]=2)=[CH:23][C:22]([Cl:21])=[CH:30][CH:29]=3)=[O:32])[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4]1)([CH3:20])([CH3:19])[CH3:18]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 181649HOAtHCID 21883477Ethylcarbodiimide hydrochlorideHCID 131726838HCID 131726838, compound

Product 1

HCID 131726839HCID 131726839, compoundYield 72.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of trans 3-amino-2-carbo-t-butoxymethoxy-1,2,3,4-tetrahydronaphthalene (550 mg, 1.98 mmol) and 5-chloroindole-2-carboxylic acid (466 mg, 2.39 mmol) in tetrahydrofuran (12 mL) at room temperature under nitrogen was added 1-[3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (760 mg, 2.39 mmol), 1-hydroxy-7-azabenzotriazole (540, 2.39 mmol), and diisopropylethylamine (0.4 mL). After 1 h, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with 1.0 M aqueous hydrochloric acid solution, 1.0 M aqueous sodium hydroxide solution and brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the resulting residue was purified by silica gel chromatography (20% ethyl acetate in hexane was used) to obtain the title compound (653 mg, 72%). 13C NMR (400 MHz, CDCl3) δ 172.31, 162.11, 134.72, 133.82, 132.8, 132.7, 128.8, 128.7, 126.6, 126.3, 125.7, 124.3, 121.0, 113.2, 102.6, 83.3, 77.6, 66.1, 51.7, 35.8, 34.4, 28.2. 1H NMR (400 MHz, CDCl3) δ 9.22 (s, 1H), 8.92 (d, J=4.0 Hz, 1H), 7.60 (s, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.22 (dd, J=2.2, 7.8 Hz, 1H), 7.07-7.19 (m, 3H), 4.27 (d, J=17.6 Hz, 1H), 4.20 (m, 1H), 4.12 (d, J=17.6 Hz, 1H), 3.91 (dd, J=4.5, 16.8 Hz, 1H), 3.76 (dt, J=5.3, 8.0 Hz, 1H), 3.24 (dd, J=5.2, 16.8 Hz, 1H), 2.92 (dd, J=9.5, 15.0 Hz, 1H), 2.77 (dd, J=9.5, 15.0 Hz, 1H). MS [M+H]+, 455; [M−H]−, 453.

Workup

  1. washThe organic layer was washed with 1.0 M aqueous hydrochloric acid solution, 1.0 M aqueous sodium hydroxide solution and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated
  4. customthe resulting residue was purified by silica gel chromatography (20% ethyl acetate in hexane was used)

Sources & evidence

ORD record
ord-0fe1307cf88c4e848af5ffb1e2e395e8
Source dataset
uspto-grants-2008_04
Patent number
US07365061B2

Reaction notes

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