Diisopropylethylamine → N-(azetidin-1-ylsulfonyl)-5-chloro-4-{[(5-chloro-6-cyclopropylpyridin-3-yl)oxy]methyl}-2-fluorobenzamide

HRID 1525654Notes

Reaction equation

HRID 1525654 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]([OH:9])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[N:57]1([S:61]([NH2:64])(=[O:63])=[O:62])[CH2:60][CH2:59][CH2:58]1>ClCCl>[N:57]1([S:61]([NH:64][C:7](=[O:9])[C:6]2[CH:10]=[C:2]([Cl:1])[C:3]([CH2:12][O:13][C:14]3[CH:15]=[N:16][C:17]([CH:21]4[CH2:23][CH2:22]4)=[C:18]([Cl:20])[CH:19]=3)=[CH:4][C:5]=2[F:11])(=[O:63])=[O:62])[CH2:60][CH2:59][CH2:58]1

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 450805661-AzetidinesulfonamideHCID 896191735-Chloro-4-(((5-chloro-6-cyclopropylpyridin-3-yl)oxy)methyl)-2-fluorobenzoic acid

Product 1

HCID 71582572N-(azetidin-1-ylsulfonyl)-5-chloro-4-{[(5-chloro-6-cyclopropylpyridin-3-yl)oxy]methyl}-2-fluorobenzamideYield 67.8%

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, 500 mg, 1.4 mmol) in dichloromethane (40 mL) was added HATU (639 mg, 1.68 mmol) and N,N-diisopropylethylamine (0.78 mL, 4.49 mmol), the mixture was left to stir for 15 minutes. Azetidine-1-sulfonamide (Preparation 19, 573 mg, 4.21 mmol) was added and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was then washed with saturated aqueous NH4Cl (30 mL) and brine (30 mL). The organic layer was dried over MgSO4 and evaporated under reduced pressure to give the crude product as an orange oil. This was purified by column chromatography on silica (eluent 1:1 heptane/EtOAc) to give the title compound as an off-white solid (450 mg, 67%).

Workup

  1. waitthe mixture was left
  2. stirringthe reaction mixture was stirred at room temperature for 18 hours
  3. washThe reaction mixture was then washed with saturated aqueous NH4Cl (30 mL) and brine (30 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. customevaporated under reduced pressure
  6. customto give the crude product as an orange oil
  7. customThis was purified by column chromatography on silica (eluent 1:1 heptane/EtOAc)

Sources & evidence

ORD record
ord-f75448d3f0aa44eaa0a8ee79a0e635e0
Source dataset
uspto-grants-2015_07
Patent number
US09085517B2

Reaction notes

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