Chloromethyl Methyl Ether → HCID 131732318, compound

HRID 2272364Notes

Reaction equation

HRID 2272364 reaction equation
[Br:1][C:2]1[C:7]([CH2:8][OH:9])=[CH:6][C:5]([N:10]([C:15]2[C:34]([CH:35]3[CH2:37][CH2:36]3)=[CH:33][C:18]3[C:19]([C:29]([NH:31][CH3:32])=[O:30])=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[O:21][C:17]=3[CH:16]=2)[S:11]([CH3:14])(=[O:13])=[O:12])=[CH:4][C:3]=1[F:38].CCN(C(C)C)C(C)C.[CH2:48](Cl)[O:49][CH3:50]>C1COCC1>[Br:1][C:2]1[C:7]([CH2:8][O:9][CH2:48][O:49][CH3:50])=[CH:6][C:5]([N:10]([C:15]2[C:34]([CH:35]3[CH2:37][CH2:36]3)=[CH:33][C:18]3[C:19]([C:29]([NH:31][CH3:32])=[O:30])=[C:20]([C:22]4[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=4)[O:21][C:17]=3[CH:16]=2)[S:11]([CH3:14])(=[O:13])=[O:12])=[CH:4][C:3]=1[F:38]

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 131732317HCID 131732317, compound

Product 1

HCID 131732318HCID 131732318, compoundYield 80.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 6-(N-(4-bromo-3-fluoro-5-(hydroxymethyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (350 mg, 0.578 mmol), DIPEA (0.303 mL, 1.734 mmol) and MOM-Cl (0.110 mL, 1.445 mmol) in THF (3.0 mL) was stirred at 50° C. in a sealed tube. After 23 hours, the solution was concentrated and purified by silica gel chromatography (0-40% EtOAc in hexanes) to give 6-(N-(4-bromo-3-fluoro-5-((methoxymethoxy)methyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (303 mg, 70% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.59 (br. s., 1H), 0.74-0.94 (m, 2H), 0.94-1.10 (m, 1H), 1.99-2.12 (m, 1H), 3.00 (d, J=4.9 Hz, 3H), 3.27 (s, 3H), 3.37 (s, 3H), 4.61 (s, 2H), 4.71 (s, 2H), 5.85 (d, J=4.6 Hz, 1H), 7.13 (dd, J=10.0, 2.7 Hz, 1H), 7.17-7.25 (m, 2H), 7.33 (d, J=1.5 Hz, 1H), 7.48 (s, 1H), 7.58 (s, 1H), 7.83-7.92 (m, 2H). LCMS (m/z, ES+)=649, 651 (M+H+).

Workup

  1. concentrationthe solution was concentrated
  2. custompurified by silica gel chromatography (0-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ffd6ffa08cee4fe69148c0f725bac6bb
Source dataset
uspto-grants-2015_09
Patent number
US09119868B2

Reaction notes

Loading…