Water → HCID 46909864, compound

HRID 2114453Notes

Reaction equation

HRID 2114453 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([Cl:47])=[CH:11][C:12]2[O:17][CH2:16][C:15](=[O:18])[N:14]([CH2:19][C:20]([N:22]([CH3:45])[C@H:23]([C:30]3[CH:35]=[CH:34][C:33]([C:36]4[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([NH2:44])=[O:43])[CH:37]=4)=[CH:32][CH:31]=3)[CH2:24][N:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)=[O:21])[C:13]=2[CH:46]=1.C(=O)(O)[O-].[Na+].O>C(OCC)(=O)C>[ClH:8].[Cl:8][C:9]1[C:10]([Cl:47])=[CH:11][C:12]2[O:17][CH2:16][C:15](=[O:18])[N:14]([CH2:19][C:20]([N:22]([CH3:45])[C@H:23]([C:30]3[CH:31]=[CH:32][C:33]([C:36]4[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([NH2:44])=[O:43])[CH:37]=4)=[CH:34][CH:35]=3)[CH2:24][N:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)=[O:21])[C:13]=2[CH:46]=1

Participants

5

Reactant 3

HCID 962WaterHCID 516892Sodium BicarbonateHCID 46846505HCID 46846505, compound2×

Product 1

HCID 46909864HCID 46909864, compoundYield 142.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

4′-[(1R)-1-[[(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-3-biphenylcarboxamide, Trifluoroacetate salt (94 mg, 0.135 mmol) was dissolved in 20 mL of ethyl acetate. A 1:1 mixture of saturated sodium bicarbonate and water was prepared separately, and 20 mL of this solution was delivered to the flask containing 4′-[(1R)-1-[[(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-3-biphenylcarboxamide, Trifluoroacetate salt. This mixture was magnetically stirred for one hour at room temperature and then the mixture was diluted with 40 mL of ethyl acetate. The organic phase was separated from the aqueous phase, dried over magnesium sulfate, filtered, and concentrated under vacuum. The resulting free base material was taken up in 1 mL of dioxane and then 2 mL of a 4M HCl/dioxane solution was slowly added. A white solid precipitated out of solution and then the flask containing the mixture was transferred to a sonicator and was sonicated for 20 minutes. The mixture was transferred to a vial and dried under vacuum to give 4′-[(1R)-1-[[(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-3-biphenylcarboxamide, Hydrochloride salt (59.3 mg, 0.096 mmol, 71%) as an off-white solid. MS (ES) m/e 583 [M+H]+

Workup

  1. customwas prepared separately
  2. customThe organic phase was separated from the aqueous phase
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. addition2 mL of a 4M HCl/dioxane solution was slowly added
  7. customA white solid precipitated out of solution
  8. additionthe flask containing the mixture
  9. customwas sonicated for 20 minutes
  10. customdried under vacuum

Sources & evidence

ORD record
ord-9863a8cf4bf64be0b38ee6f391226e7a
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

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