Diisopropylethylamine → 5-chloro-4-{[(5-chloro-6-cyclopropylpyridin-3-yl)oxyl]methyl}-N-[(dimethylamino)sulfonyl]-2-fluorobenzamide diethylamine salt

HRID 1525653Notes

Reaction equation

HRID 1525653 reaction equation
[Cl:1][C:2]1[C:3]([CH2:12][O:13][C:14]2[CH:15]=[N:16][C:17]([CH:21]3[CH2:23][CH2:22]3)=[C:18]([Cl:20])[CH:19]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7](O)=[O:8].[CH3:24][N:25]([C:27](ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.CN[N:59](NC)[SH:60](=[O:62])=[O:61]>ClCCl>[CH2:15]([NH:16][CH2:17][CH3:18])[CH3:14].[Cl:1][C:2]1[C:3]([CH2:12][O:13][C:14]2[CH:15]=[N:16][C:17]([CH:21]3[CH2:23][CH2:22]3)=[C:18]([Cl:20])[CH:19]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:59][S:60]([N:25]([CH3:27])[CH3:24])(=[O:62])=[O:61])=[O:8]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896191735-Chloro-4-(((5-chloro-6-cyclopropylpyridin-3-yl)oxy)methyl)-2-fluorobenzoic acidHCID 178486254HCID 178486254, compound

Product 1

HCID 716161505-chloro-4-{[(5-chloro-6-cyclopropylpyridin-3-yl)oxyl]methyl}-N-[(dimethylamino)sulfonyl]-2-fluorobenzamide diethylamine saltYield 18.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 5-chloro-4-(((5-chloro-6-cyclopropylpyridin-3-yl)oxy)methyl)-2-fluorobenzoic acid (Preparation 27, 200 mg, 0.56 mmol) in dichloromethane (20 mL) was added HATU (256 mg, 0.67 mmol) and diisopropylethylamine (0.30 mL, 1.79 mmol). The reaction mixture was stirred at room temperature for 15 minutes before the addition of N,N-dimethylamino sulphonamide (209 mg, 1.68 mmol). The reaction mixture was stirred under nitrogen at room temperature for 18 hours. Upon completion the reaction mixture was washed with aqueous NH4Cl (15 mL) and brine (15 mL). The organic extracts were dried (MgSO4) and evaporated under vacuum to give the crude product as an orange oil, which was purified by column chromatography on silica (eluting with 1:1 cyclohexane/EtOAc). The partially purified product was dissolved in DMSO (2 mL) and purified by reverse phase chromatography (0-90% acetonitrile/water containing 0.1% formic acid) to afford the title compound as a beige solid (28 mg, 11%).

Workup

  1. washUpon completion the reaction mixture was washed with aqueous NH4Cl (15 mL) and brine (15 mL)
  2. dry with materialThe organic extracts were dried (MgSO4)
  3. customevaporated under vacuum
  4. customto give the crude product as an orange oil, which
  5. customwas purified by column chromatography on silica (eluting with 1:1 cyclohexane/EtOAc)
  6. dissolutionThe partially purified product was dissolved in DMSO (2 mL)
  7. custompurified by reverse phase chromatography (0-90% acetonitrile/water containing 0.1% formic acid)

Sources & evidence

ORD record
ord-a33b2ad084164c6f8cb74874f1006e58
Source dataset
uspto-grants-2015_07
Patent number
US09085517B2

Reaction notes

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