Chloromethyl Methyl Ether → HCID 67410329, compound

HRID 515218Notes

Reaction equation

HRID 515218 reaction equation
[F:1][C:2]1([F:27])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[CH:22]=[C:21]([OH:23])[CH:20]=[CH:19][C:16]=3[C:17]#[N:18])=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:26])=[O:25].[H-].[Na+].[CH2:30](Cl)[O:31][CH3:32]>CN(C=O)C>[F:27][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]3[CH:22]=[C:21]([O:23][CH2:30][O:31][CH3:32])[CH:20]=[CH:19][C:16]=3[C:17]#[N:18])=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:26])=[O:25]

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 67409967HCID 67409967, compound

Product 1

HCID 67410329HCID 67410329, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-hydroxybenzonitrile (12-2) (25 mg, 0.06 mmol, 1 eq) was dissolved in anhydrous DMF (0.5 mL) and sodium hydride (3.1 mg, 0.08 mmol, 1.2 eq, 60% in oil) was added. The resulting mixture was stirred at ambient temperature for 30 minutes and MOM-Cl (0.01 mL, 0.1 mmol, 2 eq) was added. The resulting mixture stirred at ambient temperature for 10 minutes. The crude mixture was purified by reverse phase chromatography (Waters Sunfire MSC18, 10-100% acetonitrile in water with 0.1% TFA modifier) to afford 2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-(methoxymethoxy)benzonitrile (16-1) as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.68 (d, J=8.4 Hz, 1 H); 7.19 (dd, J=1.6, 8.0 Hz, 1 H); 7.11 (s, 1 H); 7.09 (dd, J=2.4, 8.8 Hz, 1 H); 6.95 (s, 1 H); 6.91 (d, J=8.0 Hz, 1 H); 5.26 (s, 2 H); 3.91 (d, J=6.8 Hz, 2 H); 3.50 (s, 3 H); 3.34 (s, 3 H); 2.11-2.19 (m, 1 H); 1.61-1.69 (m, 1 H); 1.36-1.44 (m, 1 H). LRMS m/z (M+H) 436.3 found, 436.1 required.

Workup

  1. stirringThe resulting mixture stirred at ambient temperature for 10 minutes
  2. customThe crude mixture was purified by reverse phase chromatography (Waters Sunfire MSC18, 10-100% acetonitrile in water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-f75ba31fe1c74bae802252a0acbdce79
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Reaction notes

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