Phosphorus oxychloride → HCID 86726367, compound

HRID 629761Notes

Reaction equation

HRID 629761 reaction equation
[N:1]([C@@H:4]([C@@H:8]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)[C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([F:16])[CH:10]=1)[C:5]([OH:7])=O)=[N+:2]=[N-:3].[NH2:24][C:25]1[CH:26]=[N:27][CH:28]=[C:29]([F:56])[C:30]=1[CH2:31][CH2:32][C@H:33]1[O:38][CH2:37][C@H:36]([CH2:39][O:40][C:41]([NH:43][CH2:44][C:45]([F:48])([F:47])[F:46])=[O:42])[N:35]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:34]1.O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[N:1]([C@@H:4]([C@@H:8]([C:17]1[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=1)[C:9]1[CH:10]=[C:11]([F:16])[CH:12]=[C:13]([F:15])[CH:14]=1)[C:5]([NH:24][C:25]1[CH:26]=[N:27][CH:28]=[C:29]([F:56])[C:30]=1[CH2:31][CH2:32][C@H:33]1[O:38][CH2:37][C@@H:36]([CH2:39][O:40][C:41](=[O:42])[NH:43][CH2:44][C:45]([F:48])([F:46])[F:47])[N:35]([C:49]([O:51][C:52]([CH3:54])([CH3:53])[CH3:55])=[O:50])[CH2:34]1)=[O:7])=[N+:2]=[N-:3]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 86726352HCID 86726352, compoundHCID 86726368HCID 86726368, compound

Product 1

HCID 86726367HCID 86726367, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
-10 °C

Procedure

The product from step 1 (105 mg, 0.31 mmol) and the product from step 4 of Example 89 (150 mg, 0.31 mmol) were dissolved in pyridine (1 mL) and the stirred solution was cooled to −10° C. in an ice/acetone bath. To the cold solution was added POCl3 dropwise (0.035 mL, 0.38 mmol). The mixture was stirred at −10° C. for 30 min. The reaction was quenched by the addition of saturated aqueous NaHCO3 solution (1 mL) and the mixture was allowed to warm to ambient temperature. The mixture was diluted with water (10 mL) and extracted with dichloromethane (3×10 mL). The combined dichloromethane phases were dried (Na2SO4), filtered, and the filtrate solvents were removed in vacuo. The residue was purified on a 12 g silica gel column using a gradient elution of 0-70% EtOAc:hexanes. Fractions containing product were combined and the solvents were removed in vacuo to give the title compound as a gum. (M+H)+=800.6.

Workup

  1. customThe reaction was quenched by the addition of saturated aqueous NaHCO3 solution (1 mL)
  2. temperatureto warm to ambient temperature
  3. additionThe mixture was diluted with water (10 mL)
  4. extractionextracted with dichloromethane (3×10 mL)
  5. dry with materialThe combined dichloromethane phases were dried (Na2SO4)
  6. filtrationfiltered
  7. customthe filtrate solvents were removed in vacuo
  8. customThe residue was purified on a 12 g silica gel column
  9. washa gradient elution of 0-70% EtOAc
  10. additionFractions containing product
  11. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-5e70a727fd004604adf493591c68a7de
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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