Phosphorus oxychloride → HCID 86726384, compound

HRID 629774Notes

Reaction equation

HRID 629774 reaction equation
[N:1]([C@@H:4]([C@@H:8]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([Cl:23])[CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:5](O)=[O:6])=[N+:2]=[N-:3].[NH2:24][C:25]1[CH:55]=[CH:54][CH:53]=[C:52]([F:56])[C:26]=1[CH2:27][CH2:28][C@H:29]1[O:34][CH2:33][C@@H:32]([CH2:35][O:36][C:37](=[O:44])[NH:38][CH2:39][C:40]([F:43])([F:42])[F:41])[N:31]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:30]1.O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[N:1]([C@@H:4]([C@@H:8]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([Cl:23])[CH:16]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:5]([NH:24][C:25]1[CH:55]=[CH:54][CH:53]=[C:52]([F:56])[C:26]=1[CH2:27][CH2:28][C@H:29]1[O:34][CH2:33][C@@H:32]([CH2:35][O:36][C:37](=[O:44])[NH:38][CH2:39][C:40]([F:43])([F:41])[F:42])[N:31]([C:45]([O:47][C:48]([CH3:49])([CH3:50])[CH3:51])=[O:46])[CH2:30]1)=[O:6])=[N+:2]=[N-:3]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 86726370HCID 86726370, compoundHCID 86726385HCID 86726385, compound

Product 1

HCID 86726384HCID 86726384, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
-10 °C

Procedure

The product from step 1 (151 mg, 0.45 mmol) and the product from step 4 of Example 99 (200 mg, 0.42 mmol) were dissolved in pyridine (5 mL) and the stirred solution was cooled to −10° C. in an ice/acetone bath. To the cold solution was added POCl3 dropwise (0.04 mL, 0.45 mmol). The mixture was stirred at −10° C. for 30 min. The reaction was quenched by the addition of saturated aqueous NaHCO3 solution (5 mL) and the mixture was allowed to warm to ambient temperature. The mixture was diluted with water (20 mL) and extracted with dichloromethane (3×15 mL). The combined dichloromethane extracts 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 0-100% EtOAc:hexanes. Fractions containing product were combined and the solvents were removed in vacuo to give the title compound as a gum. (M+H-N2)+=764.

Workup

  1. customThe reaction was quenched by the addition of saturated aqueous NaHCO3 solution (5 mL)
  2. temperatureto warm to ambient temperature
  3. additionThe mixture was diluted with water (20 mL)
  4. extractionextracted with dichloromethane (3×15 mL)
  5. dry with materialThe combined dichloromethane extracts 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 0-100% EtOAc
  10. additionFractions containing product
  11. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-6e99b199008a48a19c2c06735ed63909
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

Loading…