Methanesulfonamide → 5-chloro-4-({5-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluoro-N-(methylsulfonyl)benzamide

HRID 2048028Notes

Reaction equation

HRID 2048028 reaction equation
C(N(C(C)C)CC)(C)C.[Cl:10][C:11]1[C:12]([O:21][C:22]2[CH:23]=[N:24][C:25]([O:29][C@@H:30]([CH3:35])[C:31]([F:34])([F:33])[F:32])=[C:26]([Cl:28])[CH:27]=2)=[CH:13][C:14]([F:20])=[C:15]([CH:19]=1)[C:16](O)=[O:17].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[CH3:60][S:61]([NH2:64])(=[O:63])=[O:62]>ClCCl>[Cl:10][C:11]1[C:12]([O:21][C:22]2[CH:23]=[N:24][C:25]([O:29][C@@H:30]([CH3:35])[C:31]([F:34])([F:33])[F:32])=[C:26]([Cl:28])[CH:27]=2)=[CH:13][C:14]([F:20])=[C:15]([CH:19]=1)[C:16]([NH:64][S:61]([CH3:60])(=[O:63])=[O:62])=[O:17]

Participants

6

Reactant 4

HCID 72879MethanesulfonamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58042412(S)-5-chloro-4-((5-chloro-6-((1,1,1-trifluoropropan-2-yl)oxy)pyridin-3-yl)oxy)-2-fluorobenzoic acid

Product 1

HCID 566440145-chloro-4-({5-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluoro-N-(methylsulfonyl)benzamideYield 58.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diisopropylethyl amine (11.7 mL, 66.8 mmol) was added to a solution of (S)-5-chloro-4-((5-chloro-6-((1,1,1-trifluoropropan-2-yl)oxy)pyridin-3-yl)oxy)-2-fluorobenzoic acid (Preparation 299, 6.9 g, 16.7 mmol), (2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) (9.5 g, 25.1 mmol) and methylsulfonamide (2.4 g, 25.1 mmol) in dichloromethane (125 mL). The reaction mixture was stirred at room temperature for 20 hours, then quenched with an aqueous solution of hydrogen chloride (2M, 50 mL). Organics were removed in vacuo and the aqueous residue was extracted with ethyl acetate (3×100 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The crude compound was purified by silica gel chromatography, eluting with dichloromethane:methanol (from 100:0 to 96:4), followed by reverse phase chromatography, eluting with acetonitrile:water (from 5:95 to 95:5) to provide the title compound as a white solid (4.8 g, 56%).

Workup

  1. customquenched with an aqueous solution of hydrogen chloride (2M, 50 mL)
  2. customOrganics were removed in vacuo
  3. extractionthe aqueous residue was extracted with ethyl acetate (3×100 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude compound was purified by silica gel chromatography
  8. washeluting with dichloromethane
  9. washeluting with acetonitrile

Sources & evidence

ORD record
ord-ea9fbc59fdba4d54a50bdf3288012853
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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