Methyl iodide → 5-cyclopropyl-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-2-(4-methoxyphenyl)-N-methyl-2H-indazole-3-carboxamide

HRID 1037545Notes

Reaction equation

[CH:1]1([C:4]2[C:12]([N:13]([CH2:18][CH2:19][CH2:20][OH:21])[S:14]([CH3:17])(=[O:16])=[O:15])=[CH:11][C:10]3[C:6](=[C:7]([C:29]([NH:31][CH3:32])=[O:30])[N:8]([C:22]4[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=4)[N:9]=3)[CH:5]=2)[CH2:3][CH2:2]1.[C:33](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C>[CH:1]1([C:4]2[C:12]([N:13]([CH2:18][CH2:19][CH2:20][OH:21])[S:14]([CH3:17])(=[O:15])=[O:16])=[CH:11][C:10]3[C:6](=[C:7]([C:29]([NH:31][CH3:32])=[O:30])[N:8]([C:22]4[CH:23]=[CH:24][C:25]([O:28][CH3:33])=[CH:26][CH:27]=4)[N:9]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a suspension of compound (ii) (3 mg, 0.007 mmol) and potassium carbonate (3 mg, 0.022 mmol) in DMF (0.25 mL) was added iodomethane (3 μL, 0.048 mmol) and the reaction was stirred at 60° C. for 45 min. The mixture was concentrated to dryness and the residue was purified by reverse phase flash column chromatography eluting with ACN/water (5-100%) to afford Compound (55) as a white solid (2 mg, 65%). ESI-MS m/z calculated for [M+H]+: 473.2; found: 473.2; 1H NMR (400 MHz, Acetone) δ 7.86 (d, J=0.5 Hz, 1H), 7.64 (brs, 1H), 7.62-7.56 (m, 2H), 7.42 (s, 1H), 7.14-7.06 (m, 2H), 3.99-3.85 (m, 5H), 3.71-3.62 (m, 2H), 3.59 (t, J=5.2 Hz, 1H), 3.18 (s, 3H), 2.96 (d, J=4.7 Hz, 3H), 2.52-2.42 (m, 1H), 1.91-1.73 (m, 2H), 1.11-0.94 (m, 3H), 0.64-0.53 (m, 1H).

Workup

concentrationThe mixture was concentrated to dryness
customthe residue was purified by reverse phase flash column chromatography
washeluting with ACN/water (5-100%)

Sources & evidence

ORD record: ord-5b8283919d0147918d3f1f8ad0e26571
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546389B2

Reaction notes

Loading…