Methyl iodide → 5'-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(isopropoxymethyl)-N,N-dimethylbiphenyl-4-carboxamide

HRID 39178Notes

Reaction equation

HRID 39178 reaction equation
[H-].[Na+].[O:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3([C:15]([NH:17][C:18]4[CH:19]=[CH:20][C:21]([CH3:35])=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([C:30]([N:32]([CH3:34])[CH3:33])=[O:31])=[CH:26][CH:25]=5)[CH:23]=4)=[O:16])[CH2:14][CH2:13]3)=[CH:11][C:6]=2[O:5][CH2:4]1.IC>O1CCCC1.CN(C)C=O>[O:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3([C:15]([NH:17][C:18]4[CH:19]=[CH:20][C:21]([CH2:35][O:3][CH:7]([CH3:8])[CH3:6])=[C:22]([C:24]5[CH:25]=[CH:26][C:27]([C:30]([N:32]([CH3:34])[CH3:33])=[O:31])=[CH:28][CH:29]=5)[CH:23]=4)=[O:16])[CH2:14][CH2:13]3)=[CH:11][C:6]=2[O:5][CH2:4]1

Participants

6

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 592065844-[5-(1-benzo[1,3]dioxol-5-ylcyclopropyl)carbonylamino-2-methyl-phenyl]-N,N-dimethyl-benzamide

Product 1

HCID 592066525'-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(isopropoxymethyl)-N,N-dimethylbiphenyl-4-carboxamideYield 75.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (2.2 mg, 0.055 mmol, 60% by weight dispersion in oil) was slowly added to a stirred solution of 5′(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-N,N,2′-trimethylbiphenyl-4-carboxamide (21 mg, 0.048 mmol) in a mixture of 0.90 mL of anhydrous tetrahydrofuran (THF) and 0.10 mL of anhydrous N,N-dimethylformamide (DMF). The resulting suspension was allowed to stir for 3 minutes before iodomethane (0.0048 mL, 0.072 mmol) was added to the reaction mixture. An additional aliquot of sodium hydride and iodomethane were required to consume all of the starting material which was monitored by LCMS. The crude reaction product was evaporated to dryness, redissolved in a minimum of DMF and purified by preparative LCMS chromatography to yield 5′-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2′-(isopropoxymethyl)-N,N-dimethylbiphenyl-4-carboxamide (9.1 mg, 42%) ESI-MS m/z calc. 456.2, found 457.5 (M+1)+. Retention time of 2.94 minutes. 1H-NMR (400 MHz, CD3CN) δ 0.91-0.93 (m, 2H), 1.41-1.45 (m, 2H), 2.23 (s, 3H), 3.00 (s, 3H), 3.07 (s, 3H), 3.20 (s, 3H), 5.81 (s, 2H), 6.29-6.36 (m, 2H), 6.56 (d, J=8.0 Hz, 1H), 6.69 (s, 1H), 6.92 (dd, J=1.6, 7.9 Hz, 1H), 7.17 (d, J=8.1 Hz, 1H), 7.28 (d, J=8.1 Hz, 2H), 7.46 (dd, J=1.8, 6.4 Hz, 2H).

Workup

  1. additionwas added to the reaction mixture
  2. customto consume all of the starting material which
  3. customThe crude reaction product
  4. customwas evaporated to dryness
  5. dissolutionredissolved in a minimum of DMF
  6. custompurified by preparative LCMS chromatography

Sources & evidence

ORD record
ord-20c6adca01234c00865c95a81a49209c
Source dataset
uspto-grants-2013_09
Patent number
US08524767B2

Reaction notes

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