Pyridine → HCID 59394958, compound

HRID 383431Notes

Reaction equation

HRID 383431 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH:10]([C:12]([OH:14])=O)[CH2:9][N:8]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:7]=2[CH:20]=1)#[N:2].C(=O)([O-])OC[C:24]1[CH:29]=[C:28]([NH2:30])[C:27]([Br:31])=[CH:26][C:25]=1[CH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1.N1C=CC=CC=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)[O:49]1)CC.[C:63]([O:66][CH2:67]C)(=[O:65])C>CC1CCCO1>[Br:31][C:27]1[CH:26]=[C:25]([CH:32]2[CH2:33][CH2:34][CH2:35][CH2:36]2)[C:24]([O:65][C:63]([O:66][CH3:67])=[O:49])=[CH:29][C:28]=1[NH:30][C:12]([CH:10]1[O:11][C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:20][C:7]=2[N:8]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:9]1)=[O:14]

Participants

7

Reactant 5

HCID 1049PyridineHCID 8857Ethyl AcetateHCID 111923Propylphosphonic anhydrideHCID 593949876-Cyano-4-ethoxycarbonyl-2,3-dihydro-1,4-benzoxazine-2-carboxylic acidHCID 131730194(5-Amino-4-bromo-2-cyclopentyl-phenyl)methyl carbonate

Product 1

HCID 59394958HCID 59394958, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

To a solution of 6-cyano-4-ethoxycarbonyl-2,3-dihydro-1,4-benzoxazine-2-carboxylic acid (552 mg, 2.0 mmol) and (5-amino-4-bromo-2-cyclopentyl-phenyl)methyl carbonate (691 mg, 2.20 mmol) in 2-methyltetrahydrofuran (7 mL) at room temperature was added pyridine (404 μL, 5.0 mmol) followed by the addition of T3P (3181 mg, 2.98 mL of 50% w/w solution, 5.0 mmol). The reaction was stirred at room temperature for 1 h. The reaction mixture was diluted with ethyl acetate then quenched with a saturated aqueous solution of NaHCO3 (4 mL) and stirred for 15 min. The layers were separated, and the aqueous layer was extracted once more with ethyl acetate. The combined organic extracts were filtered to give a white solid. The remaining filtrate was dried over Na2SO4, filtered and concentrated in vacuo to obtain a creamy solid. The combined solids were triturated with hexane (5×5 mL) and washed with ethyl acetate (1 mL) and dichloromethane (1 mL) to provide ethyl 2-(2-bromo-4-cyclopentyl-5-(methoxycarbonyloxy)phenylcarbamoyl)-6-cyano-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate as a white solid (403 mg, 99% yield). LC/MS m/z 573.1 [M+H]+.

Workup

  1. customthen quenched with a saturated aqueous solution of NaHCO3 (4 mL)
  2. stirringstirred for 15 min
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted once more with ethyl acetate
  5. filtrationThe combined organic extracts were filtered
  6. customto give a white solid
  7. dry with materialThe remaining filtrate was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto obtain a creamy solid
  11. customThe combined solids were triturated with hexane (5×5 mL)
  12. washwashed with ethyl acetate (1 mL) and dichloromethane (1 mL)

Sources & evidence

ORD record
ord-779712eac7374981886fc23fcbddc9e6
Source dataset
uspto-grants-2013_02
Patent number
US08367660B2

Reaction notes

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