Pyridine → Tert-butyl 6-[[2-(4-cyclopropylsulfonylphenyl)-2-(2,4-difluorophenoxy)acetyl]amino]pyridine-3-carboxylate

HRID 524428Notes

Reaction equation

HRID 524428 reaction equation
[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[F:25])[C:14]([OH:16])=O)=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:37][C:38]1[N:43]=[CH:42][C:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])=[CH:40][CH:39]=1.N1C=CC=CC=1>C(Cl)Cl>[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[F:25])[C:14]([NH:37][C:38]3[N:43]=[CH:42][C:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])=[CH:40][CH:39]=3)=[O:16])=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 1049PyridineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 22054350Tert-butyl 6-aminopyridine-3-carboxylateHCID 596100322-(4-Cyclopropylsulfonylphenyl)-2-(2,4-difluorophenoxy)acetic acid

Product 1

HCID 68182669Tert-butyl 6-[[2-(4-cyclopropylsulfonylphenyl)-2-(2,4-difluorophenoxy)acetyl]amino]pyridine-3-carboxylateYield 54.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

2-(4-cyclopropylsulfonylphenyl)-2-(2,4-difluorophenoxy)acetic acid (Preparation 1; 2.0 g, 5.42 mmol) was dissolved in DCM (20 mL). To this solution was added DMF (0.41 mL, 5.42 mmol) and cooled to 0° C., followed by the addition of oxalyl chloride (0.77 mL, 8.14 mmol) and further stirred for 1 hr at room temp. To this mixture, a solution of tert-butyl 6-aminopyridine-3-carboxylate (preparation 54, 1.26 g, 6.51 mmol) and pyridine (2.19 mL, 2.71 mmol) in DCM 20 (mL) was added drop wise at 0° C. and was stirred further for 1 hr at room temperature. The reaction mixture was diluted with DCM (50 mL), organic layer was washed with water, followed by brine, dried over anhydrous sodium sulfate, solvent was removed under reduced pressure to get the crude compound which was purified by silica gel column chromatography to get the title product (1.6 g).

Workup

  1. stirringwas stirred further for 1 hr at room temperature
  2. washwas washed with water
  3. dry with materialdried over anhydrous sodium sulfate, solvent
  4. customwas removed under reduced pressure
  5. customto get the crude compound which
  6. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d23982a6fb1d4c63a8251a040a2e3c41
Source dataset
uspto-grants-2016_05
Patent number
US09340506B2

Reaction notes

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