Pyridine → HCID 59394958, compound

HRID 472002Notes

Reaction equation

HRID 472002 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:21](=[O:38])([O:36][CH3:37])[O:22][C:23]1[CH:28]=[C:27]([NH2:29])[C:26]([Br:30])=[CH:25][C:24]=1[CH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1.N1C=CC=CC=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CC1CCCO1.C(OCC)(=O)C>[Br:30][C:26]1[CH:25]=[C:24]([CH:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)[C:23]([O:22][C:21]([O:36][CH3:37])=[O:38])=[CH:28][C:27]=1[NH:29][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 4

HCID 1049PyridineHCID 111923Propylphosphonic anhydrideHCID 59394974HCID 59394974, compoundHCID 593949876-Cyano-4-ethoxycarbonyl-2,3-dihydro-1,4-benzoxazine-2-carboxylic acid

Product 1

HCID 59394958HCID 59394958, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 73012-MethyltetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

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-3eb33d0b515a4c71a1673f8eafe5c88a
Source dataset
uspto-grants-2014_01
Patent number
US08633189B2

Reaction notes

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