Tetrahydrofuran → HCID 21949992, compound

HRID 2215822Notes

Reaction equation

[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH2:11][C:12]([NH2:14])=[O:13])[CH:4]=[CH:3]1.[F:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][CH:20]=[C:19]2[C:25](=O)[C:26](OC)=[O:27].CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[F:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][CH:20]=[C:19]2[C:25]1[C:26](=[O:27])[NH:14][C:12](=[O:13])[C:11]=1[C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[N:2]([CH3:1])[CH:3]=[CH:4]2

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of 2-(1-methyl-1H-indol-7-yl)acetamide (350 mg, 1.86 mmol) and methyl 2-(5-fluoro-1H-indol-3-yl)oxoacetate (427 mg, 1.93 mmol) in DMF (25 mL) was added a 1.0 M solution of potassium tert-butoxide in THF (6.5 mL, 6.5 mmol) at room temperature under N2. The reaction was heated to 65° C. and stirred for 20 h at this temperature. The reaction mixture was then cooled to room temperature and quenched with 1.0 N hydrochloric acid, extracted with EtOAc (50 mL), washed with H2O (2×30 mL), saturated NaCl (2×30 mL), dried (MgSO4), filtered and concentrated. Flash chromatography (SiO2, 30% EtOAc/hexanes) gave the title compound (282 mg, 42%) as a maroon solid, mp 230° C. dec. 1H NMR (DMSO-d6) δ 11.95 (bs, 1H), 11.18 (bs, 1H), 7.98 (s, 1H), 7.64 (m, 1H), 7.34 (m, 1H), 7.28 (m, 1H), 6.99 (m, 1H), 6.92 (m, 1H), 6.83 (m, 1H), 6.48 (m, 1H), 5.91 (m, 1H), 3.67 (s, 3H). MS (APCI): m/z=360 [C21H14FN3O2+H]+

Workup

temperatureThe reaction mixture was then cooled to room temperature
customquenched with 1.0 N hydrochloric acid
extractionextracted with EtOAc (50 mL)
washwashed with H2O (2×30 mL), saturated NaCl (2×30 mL)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-3103761ba525402b9b04fba979b62e58
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07109229B2

Reaction notes

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