Chloromethyl Methyl Ether → HCID 131732303, compound

HRID 1424856Notes

Reaction equation

HRID 1424856 reaction equation
Cl[CH2:2][O:3][CH3:4].[Br:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]([C:17]2[C:36]([CH:37]3[CH2:39][CH2:38]3)=[CH:35][C:20]3[C:21]([C:31]([NH:33][CH3:34])=[O:32])=[C:22]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[O:23][C:19]=3[CH:18]=2)[S:13]([CH3:16])(=[O:15])=[O:14])=[CH:8][C:7]=1[CH2:40][OH:41].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>O1CCCC1>[Br:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]([C:17]2[C:36]([CH:37]3[CH2:39][CH2:38]3)=[CH:35][C:20]3[C:21]([C:31]([NH:33][CH3:34])=[O:32])=[C:22]([C:24]4[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=4)[O:23][C:19]=3[CH:18]=2)[S:13]([CH3:16])(=[O:15])=[O:14])=[CH:8][C:7]=1[CH2:40][O:41][CH2:2][O:3][CH3:4]

Participants

6

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 131732302HCID 131732302, compound

Product 1

HCID 131732303HCID 131732303, compoundYield 97.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Chloro(methoxy)methane (0.201 mL, 2.65 mmol) was added dropwise to a solution of 6-(N-(4-bromo-3-(hydroxymethyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (0.724 g, 1.06 mmol) and DIEA (0.555 mL, 3.18 mmol) in tetrahydrofuran (10 mL) under N2. The mixture was heated to 50° C. overnight. Cooled down to room temperature and aqueous NaHCO3 was added, the aqueous layer was extracted with EtOAc (2×). The organic phase was washed with brine, dried over Na2SO4. The crude residue was purified by chromatography on silica gel eluted with 0-50% EtOAC in hexane to give the product (0.65 g, 97%) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.90 (dd, J=8.78, 5.27 Hz, 2H) 7.64 (s, 1H) 7.57 (d, J=2.73 Hz, 1H) 7.50 (d, J=8.78 Hz, 1H) 7.47 (s, 1H) 7.18-7.26 (m, 3H) 5.79 (d, J=4.49 Hz, 1H) 4.74 (s, 2H) 4.61 (s, 2H) 3.39 (s, 3H) 3.25 (s, 3H) 3.01 (d, J=4.88 Hz, 3H) 2.08-2.18 (m, 1H) 0.75-1.14 (m, 3H) 0.58 (br. s., 1H). LCMS (m/z, ES+)=633 (M+H+).

Workup

  1. temperatureCooled down to room temperature
  2. extractionthe aqueous layer was extracted with EtOAc (2×)
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. customThe crude residue was purified by chromatography on silica gel
  6. washeluted with 0-50% EtOAC in hexane

Sources & evidence

ORD record
ord-ee0a24914a864e5c8a3942feed6717da
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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