Pyridine → N-(3-(5-(4-chlorophenyl)-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide

HRID 1747258Notes

Reaction equation

HRID 1747258 reaction equation
[NH2:1][C:2]1[C:3]([F:37])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=4)[CH:18]=3)[N:13]([C:27](=[O:36])[C:28]3[C:33]([Cl:34])=[CH:32][CH:31]=[CH:30][C:29]=3[Cl:35])[CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1.N1C=CC=CC=1.[CH2:44]([S:47](Cl)(=[O:49])=[O:48])[CH2:45][CH3:46].CC1CCCO1>CN(C1C=CC=CN=1)C.O>[Cl:26][C:23]1[CH:22]=[CH:21][C:20]([C:17]2[CH:18]=[C:19]3[C:11]([C:9]([C:4]4[C:3]([F:37])=[C:2]([NH:1][S:47]([CH2:44][CH2:45][CH3:46])(=[O:49])=[O:48])[CH:7]=[CH:6][C:5]=4[F:8])=[O:10])=[CH:12][N:13]([C:27](=[O:36])[C:28]4[C:33]([Cl:34])=[CH:32][CH:31]=[CH:30][C:29]=4[Cl:35])[C:14]3=[N:15][CH:16]=2)=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 73012-MethyltetrahydrofuranHCID 662791-Propanesulfonyl chlorideHCID 72549402(3-Amino-2,6-difluoro-phenyl)-[5-(4-chlorophenyl)-1-(2,6-dichlorobenzoyl)pyrrolo[2,3-b]pyridin-3-yl]methanone

Product 1

HCID 51001026N-(3-(5-(4-chlorophenyl)-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamideYield 116.9%

Reagents, catalysts & solvents 2

HCID 218852-DimethylaminopyridineCatalystHCID 962WaterSolvent

Conditions

Temperature
12.5 °C

Procedure

Compound 7 (800 g; 1.44 mol) and dimethylamino pyridine (7.2 g; 0.059 mol), under nitrogen, were added to a 5 L three-necked-round bottom flask cooled in an ice water bath. Anhydrous pyridine (1.8 L) was charged and the mixture was stirred at 10-15° C. until a homogeneous solution was obtained. Propane-1-sulfonyl chloride (308 g; 2.16 mol) was added drop-wise from an addition funnel while keeping the reaction temperature <20° C. and the reaction mixture was stirred at 20-25° C. for 3 h. The reaction mixture was added to a mixture of 2-methyl-THF (7 L) and water (10 L) in a flask and the organic layer was separated, washed with 1N HCl (2 L) followed by brine (2 L), and dried. The residue was azeotroped with toluene to remove the residual water to provide crude compound 9 (1116.4 g) which was used in the next step without purification.

Workup

  1. temperaturecooled in an ice water bath
  2. customwas obtained
  3. customthe reaction temperature <20° C.
  4. stirringthe reaction mixture was stirred at 20-25° C. for 3 h
  5. customthe organic layer was separated
  6. washwashed with 1N HCl (2 L)
  7. customdried
  8. customThe residue was azeotroped with toluene
  9. customto remove the residual water

Sources & evidence

ORD record
ord-c08eecd5b003469c902a884c09bc60c4
Source dataset
uspto-grants-2015_10
Patent number
US09150570B2

Reaction notes

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