Phosphorus oxychloride → (S)-N-(1-(6-chloro-3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2,2,2-trifluoroacetamide

HRID 2170397Notes

Reaction equation

HRID 2170397 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([C@@H:18]([NH:28][C:29](=[O:34])[C:30]([F:33])([F:32])[F:31])[CH2:19][C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=3)=[N+:13]([O-])[CH:14]=[CH:15][CH:16]=2)=[C:7]2[C:3]=1[C:4]([NH:36][S:37]([CH3:40])(=[O:39])=[O:38])=[N:5][N:6]2[CH3:35].O=P(Cl)(Cl)[Cl:43]>>[Cl:43][C:14]1[N:13]=[C:12]([C@@H:18]([NH:28][C:29](=[O:34])[C:30]([F:33])([F:32])[F:31])[CH2:19][C:20]2[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=2)[C:11]([C:8]2[CH:9]=[CH:10][C:2]([Cl:1])=[C:3]3[C:7]=2[N:6]([CH3:35])[N:5]=[C:4]3[NH:36][S:37]([CH3:40])(=[O:38])=[O:39])=[CH:16][CH:15]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 90281489(S)-3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)-2-(2-(3,5-difluorophenyl)-1-(2,2,2-trifluoroacetamido)ethyl)pyridine 1-oxide

Product 1

HCID 90281429(S)-N-(1-(6-chloro-3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2,2,2-trifluoroacetamide

Conditions

Temperature
115 °C

Procedure

(S)-3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)-2-(2-(3,5-difluorophenyl)-1-(2,2,2-trifluoroacetamido)ethyl)pyridine 1-oxide (57C, 1.0 g, 1.66 mmol) was treated with POCl3 (2.32 mL, 24.84 mmol). The reaction mixture was stirred at 115° C. for 2 hours. Upon cooling, the reaction was concentrated in vacuo, taken in DCM, and vigorously stirred with saturated aqueous NaHCO3 for 1 hour. The organic layer was collected, and the aqueous layer was extracted an additional time with DCM. The combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo, and purified by silica gel column chromatography, eluting with 0-100% EtOAc in hexanes to give the title compound. MS (m/z) 622.13 [M+H]+.

Workup

  1. temperatureUpon cooling
  2. concentrationthe reaction was concentrated in vacuo
  3. stirringvigorously stirred with saturated aqueous NaHCO3 for 1 hour
  4. customThe organic layer was collected
  5. extractionthe aqueous layer was extracted an additional time with DCM
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by silica gel column chromatography
  10. washeluting with 0-100% EtOAc in hexanes

Sources & evidence

ORD record
ord-6cd3297cc01646aaa1f5e8b1c5e3dab9
Source dataset
uspto-grants-2015_06
Patent number
US09050344B2

Reaction notes

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