Chloromethyl Methyl Ether → 6-(N-(3-chloro-4-(3-(methoxymethoxy)prop-1-en-2-yl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1424872Notes

Reaction equation

HRID 1424872 reaction equation
Cl[CH2:2][O:3][CH3:4].[Cl:5][C:6]1[CH:7]=[C:8]([N:16]([C:21]2[C:40]([CH:41]3[CH2:43][CH2:42]3)=[CH:39][C:24]3[C:25]([C:35]([NH:37][CH3:38])=[O:36])=[C:26]([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[O:27][C:23]=3[CH:22]=2)[S:17]([CH3:20])(=[O:19])=[O:18])[CH:9]=[CH:10][C:11]=1[C:12]([CH2:14][OH:15])=[CH2:13].CCN(C(C)C)C(C)C>ClCCl>[Cl:5][C:6]1[CH:7]=[C:8]([N:16]([C:21]2[C:40]([CH:41]3[CH2:42][CH2:43]3)=[CH:39][C:24]3[C:25]([C:35]([NH:37][CH3:38])=[O:36])=[C:26]([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[O:27][C:23]=3[CH:22]=2)[S:17]([CH3:20])(=[O:19])=[O:18])[CH:9]=[CH:10][C:11]=1[C:12]([CH2:14][O:15][CH2:2][O:3][CH3:4])=[CH2:13]

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 1317323206-(N-(3-chloro-4-(3-hydroxyprop-1-en-2-yl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

Product 1

HCID 1317323216-(N-(3-chloro-4-(3-(methoxymethoxy)prop-1-en-2-yl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamideYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Methyl chloromethyl ether (0.024 mL, 0.321 mmol) was added to a mixture of 6-(N-(3-chloro-4-(3-hydroxyprop-1-en-2-yl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (83 mg, 0.146 mmol) and DIEA (0.076 mL, 0.438 mmol) in dichloromethane (2 mL). The mixture was stirred at room temperature for 1.5 hours. The reaction mixture was diluted with dichloromethane and washed with water and brine, dried over sodium sulfate and concentrated to give 6-(N-(3-chloro-4-(3-(methoxymethoxy)prop-1-en-2-yl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide as a white foam (76 mg, 85%). 1H NMR (400 MHz, chloroform-d) δ ppm 7.89 (dd, J=8.78, 5.27 Hz, 2H) 7.60 (s, 1H) 7.48 (s, 1H) 7.38 (d, J=2.15 Hz, 1H) 7.26-7.31 (m, 1H) 7.16-7.24 (m, 2H) 5.77-5.94 (m, 1H) 5.56 (s, 1H) 5.31 (s, 1H) 5.22 (s, 1H) 4.65 (s, 2H) 4.34 (s, 2H) 3.33 (s, 3H) 3.27 (s, 3H) 3.00 (d, J=4.88 Hz, 3H) 1.87-2.29 (m, 1H) 0.14-1.47 (m, 4H). LCMS (m/z, ES+)=613 (M+H+).

Workup

  1. washwashed with water and brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-c3fed7e0f4f94e1da2856e2ae30504be
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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