(3-Methoxyphenyl)acetic acid → N-(4-(1H-pyrrolo[2,3-b]pyridin-3-yl)thiophen-2-yl)-2-(3-methoxyphenyl)acetamide

HRID 2108749Notes

Reaction equation

C1(C)C=CC(S(N2C3=NC=CC=C3C(C3C=C(N)SC=3)=C2)(=O)=O)=CC=1.COC1C=C(CC(O)=O)C=CC=1.[CH3:38][O:39][C:40]1[CH:41]=[C:42]([CH2:46][C:47]([NH:49][C:50]2[S:51][CH:52]=[C:53]([C:55]3[C:63]4[C:58](=[N:59][CH:60]=[CH:61][CH:62]=4)[N:57](S(C4C=CC(C)=CC=4)(=O)=O)[CH:56]=3)[CH:54]=2)=[O:48])[CH:43]=[CH:44][CH:45]=1.O[Li].O>C1COCC1.O.CCOC(C)=O>[NH:57]1[C:58]2=[N:59][CH:60]=[CH:61][CH:62]=[C:63]2[C:55]([C:53]2[CH:54]=[C:50]([NH:49][C:47](=[O:48])[CH2:46][C:42]3[CH:43]=[CH:44][CH:45]=[C:40]([O:39][CH3:38])[CH:41]=3)[S:51][CH:52]=2)=[CH:56]1

Participants

Conditions

Temperature: 150 °C

Procedure

4-[1-(Toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-thiophen-2-ylamine was coupled to 3-methoxyphenylacetic acid according to General Method B and the product 2-(3-methoxyphenyl)-N-(4-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)thiophen-2-yl)acetamide (70 mg, 0.14 mmol) was dissolved in 6 mL THF and LiOH hydrate (63 mg, 1.5 mmol) was added in 1 mL of water. The reaction mixture was heated to 150° C. by microwave irradiation for 15 minutes and then diluted with EtOAc and water and the organic layer dried over sodium sulfate and concentrated to an oil, which was purified by column chromatography on silica (40 to 100% EtOAc/hexanes to give 20 mg of a light brown solid, 0.055 mmol, 39%. 1H NMR 500 MHz (DMSO-d6) 11.80 (1H, s), 11.37 (1H, s) 8.28 (2H, m), 7.78 (1H, s), 7.25 (1H, t), 7.16 (2H, m), 7.07 (1H, s) 6.88 (2H, m), 6.82 (1H, m), 3.78 (3H, s), 3.69 (2H, s). MH+ 364.20.

Workup

dry with materialthe organic layer dried over sodium sulfate
concentrationconcentrated to an oil, which
customwas purified by column chromatography on silica (40 to 100% EtOAc/hexanes

Sources & evidence

ORD record: ord-c305b37ca2a549e591717cc0c0b8d273
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07514448B2

Reaction notes

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